Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation

International Nuclear Information System (INIS)

Magae, J.; Furikawa, C.; Hoshi, Y.; Kawakami, Y.; Ogata, H.

2004-01-01

It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure

Biological effects of low-dose ionizing radiation exposure

International Nuclear Information System (INIS)

Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

2009-01-01

The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

Dose estimation by biological methods

International Nuclear Information System (INIS)

Guerrero C, C.; David C, L.; Serment G, J.; Brena V, M.

1997-01-01

The human being is exposed to strong artificial radiation sources, mainly of two forms: the first is referred to the occupationally exposed personnel (POE) and the second, to the persons that require radiological treatment. A third form less common is by accidents. In all these conditions it is very important to estimate the absorbed dose. The classical biological dosimetry is based in the dicentric analysis. The present work is part of researches to the process to validate the In situ Fluorescent hybridation (FISH) technique which allows to analyse the aberrations on the chromosomes. (Author)

Biphasic dose responses in biology, toxicology and medicine: Accounting for their generalizability and quantitative features

International Nuclear Information System (INIS)

Calabrese, Edward J.

2013-01-01

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30–60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying “upstream” mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. -- Highlights: •The hormetic stimulation is at maximum 30–60% greater than control responses. •Hormesis is a measure of biological performance and plasticity. •The hormetic response is evolutionary based and highly generalizable. -- This paper provides a biologically based explanation for the generalizability/quantitative features of the hormetic dose response, representing a fundamental contribution to the field

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

Science.gov (United States)

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

Review of low dose-rate epidemiological studies and biological mechanisms of dose-rate effects on radiation induced carcinogenesis

International Nuclear Information System (INIS)

Iwasaki, Toshiyasu; Otsuka, Kensuke; Yoshida, Kazuo

2015-01-01

Radiation protection system adopts the linear non-threshold model with using dose and dose-rate effectiveness factor (DDREF). The dose-rate range where DDREF is applied is below 100 mGy per hour, and it is regarded that there are no dose-rate effects at very low dose rate, less than of the order of 10 mGy per year, even from the biological risk evaluation model based on cellular and molecular level mechanisms for maintenance of genetic integrity. Among low dose-rate epidemiological studies, studies of residents in high natural background areas showed no increase of cancer risks at less than about 10 mGy per year. On the other hand, some studies include a study of the Techa River cohort suggested the increase of cancer risks to the similar degree of Atomic bomb survivor data. The difference of those results was supposed due to the difference of dose rate. In 2014, International Commission on Radiological Protection opened a draft report on stem cell biology for public consultations. The report proposed a hypothesis based on the new idea of stem cell competition as a tissue level quality control mechanism, and suggested that it could explain the dose-rate effects around a few milligray per year. To verify this hypothesis, it would be needed to clarify the existence and the lowest dose of radiation-induced stem cell competition, and to elucidate the rate of stem cell turnover and radiation effects on it. As for the turnover, replenishment of damaged stem cells would be the important biological process. It would be meaningful to collect the information to show the difference of dose rates where the competition and the replenishment would be the predominant processes. (author)

Detection of base damage in DNA in human blood exposed to ionizing radiation at biologically relevant doses

International Nuclear Information System (INIS)

Loon, A.A.W.M. van; Lohman, P.H.M.; Groenendijk, R.H.; Schans, G.P. van der; Baan, R.A.

1991-01-01

The alkaline elution technique for the detection of DNA damage has been adapted to allow application on unlabelled blood cells. Both the induction and subsequent repair have been studied of two classes of DNA damage, viz. single-strand breaks and base damage recognized by the γ-endonuclease activity in a cell-free extract of Micrococcus luteus bacteria. The high sensitivity of the assay permitted the measurement of induction and repair of base damage after in vitro exposure of full blood under aerobic conditions to biologically relevant doses of γ-rays (1.5-4.5 Gy). After a radiation dose of 3 Gy about 50% of the base damage was removed within 1.5 h of repair. Base damage could still be detected at 24h after exposure to 15 Gy. (author)

Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

International Nuclear Information System (INIS)

Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

2003-01-01

Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk

A Paradigm Shift in Low Dose Radiation Biology

Directory of Open Access Journals (Sweden)

Z. Alatas

2015-08-01

Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

Modelling the Influence of Shielding on Physical and Biological Organ Doses

CERN Document Server

Ballarini, Francesca; Ferrari, Alfredo; Ottolenghi, Andrea; Pelliccioni, Maurizio; Scannicchio, Domenico

2002-01-01

Distributions of "physical" and "biological" dose in different organs were calculated by coupling the FLUKA MC transport code with a geometrical human phantom inserted into a shielding box of variable shape, thickness and material. While the expression "physical dose" refers to the amount of deposited energy per unit mass (in Gy), "biological dose" was modelled with "Complex Lesions" (CL), clustered DNA strand breaks calculated in a previous work based on "event-by-event" track-structure simulations. The yields of complex lesions per cell and per unit dose were calculated for different radiation types and energies, and integrated into a version of FLUKA modified for this purpose, allowing us to estimate the effects of mixed fields. As an initial test simulation, the phantom was inserted into an aluminium parallelepiped and was isotropically irradiated with 500 MeV protons. Dose distributions were calculated for different values of the shielding thickness. The results were found to be organ-dependent. In most ...

Biological evidence of low ionizing radiation doses

International Nuclear Information System (INIS)

Mirsch, Johanna

2017-01-01

Throughout life, every person is constantly exposed to different types of ionising radiation, without even noticing the exposure. The mean radiation exposure for people living in Germany amounts to approximately 4 mSv per year and encompasses the exposure from natural and man-made sources. The risks associated with exposure to low doses of radiation are still the subject of intense and highly controversial discussions, emphasizing the social relevance of studies investigating the effects of low radiation doses. In this thesis, DNA double-strand breaks (DSBs) were analyzed within three projects covering different aspects. DSBs are among the most hazardous DNA lesions induced by ionizing radiation, because this type of damage can easily lead to the loss of genetic information. Consequently, the DSB presents a high risk for the genetic integrity of the cell. In the first project, extensive results uncovered the track structure of charged particles in a biological model tissue. This provided the first biological data that could be used for comparison with data that were measured or predicted using theoretical physical dosimetry methods and mathematical simulations. Charged particles contribute significantly to the natural radiation exposure and are used increasingly in cancer radiotherapy because they are more efficient in tumor cell killing than X- or γ-rays. The difference in the biological effects of high energy charged particles compared with X- or γ-rays is largely determined by the spatial distribution of their energy deposition and the track structure inducing a three-dimensional damage pattern in living cells. This damage pattern consists of cells directly hit by the particle receiving a high dose and neighboring cells not directly hit by primary particles but exposed to far-reaching secondary electrons (δ-electrons). These cells receive a much lower dose deposition in the order of a few mGy. The radial dose distribution of single particle tracks was

Mathematical model for evaluation of dose-rate effect on biological responses to low dose γ-radiation

International Nuclear Information System (INIS)

Ogata, H.; Kawakami, Y.; Magae, J.

2003-01-01

Full text: To evaluate quantitative dose-response relationship on the biological response to radiation, it is necessary to consider a model including cumulative dose, dose-rate and irradiation time. In this study, we measured micronucleus formation and [ 3 H] thymidine uptake in human cells as indices of biological response to gamma radiation, and analyzed mathematically and statistically the data for quantitative evaluation of radiation risk at low dose/low dose-rate. Effective dose (ED x ) was mathematically estimated by fitting a general function of logistic model to the dose-response relationship. Assuming that biological response depends on not only cumulative dose but also dose-rate and irradiation time, a multiple logistic function was applied to express the relationship of the three variables. Moreover, to estimate the effect of radiation at very low dose, we proposed a modified exponential model. From the results of fitting curves to the inhibition of [ 3 H] thymidine uptake and micronucleus formation, it was obvious that ED 50 in proportion of inhibition of [ 3 H] thymidine uptake increased with longer irradiation time. As for the micronuclei, ED 30 also increased with longer irradiation times. These results suggest that the biological response depends on not only total dose but also irradiation time. The estimated response surface using the three variables showed that the biological response declined sharply when the dose-rate was less than 0.01 Gy/h. These results suggest that the response does not depend on total cumulative dose at very low dose-rates. Further, to investigate the effect of dose-rate within a wider range, we analyzed the relationship between ED x and dose-rate. Fitted curves indicated that ED x increased sharply when dose-rate was less than 10 -2 Gy/h. The increase of ED x signifies the decline of the response or the risk and suggests that the risk approaches to 0 at infinitely low dose-rate

The relative biological effectiveness of out-of-field dose

International Nuclear Information System (INIS)

Balderson, Michael; Koger, Brandon; Kirkby, Charles

2016-01-01

Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions. (paper)

Biological impact of high-dose and dose-rate radiation exposure

International Nuclear Information System (INIS)

Maliev, V.; Popov, D.; Jones, J.; Gonda, S.; Prasad, K.; Viliam, C.; Haase, G.; Kirchin, V.; Rachael, C.

2006-01-01

Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

Biological impact of high-dose and dose-rate radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Maliev, V.; Popov, D. [Russian Academy of Science, Vladicaucas (Russian Federation); Jones, J.; Gonda, S. [NASA -Johnson Space Center, Houston (United States); Prasad, K.; Viliam, C.; Haase, G. [Antioxida nt Research Institute, Premier Micronutrient Corporation, Novato (United States); Kirchin, V. [Moscow State Veterinary and Biotechnology Acade my, Moscow (Russian Federation); Rachael, C. [University Space Research Association, Colorado (United States)

2006-07-01

Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

Biology of dose rate in brachytherapy

International Nuclear Information System (INIS)

Brenner, David J.

1995-01-01

Purpose: This course is designed for practitioners and beginners in brachytherapy. The aim is to review biological principles underlying brachytherapy, to understand why current treatment regimes are the way they are, and to discuss what the future may hold in store. Brachytherapy has a long history. It was suggested as long ago as 1903 by Alexander Graham Bell, and the optimal application of this technique has been a subject of debate ever since. 'Brachy' means 'short', and the essential features of conventional brachytherapy are: positioning of the source a short distance from, or in, the tumor, allowing good dose distributions; short overall treatment times, to counter tumor repopulation; low dose rate, enabling a good therapeutic advantage between tumor control and damage to late-responding tissue. The advantages of good dose distributions speak for themselves; in some situations, as we shall see, computer-based dose optimization can be used to improve them still further. The advantages of short overall times stem from the fact that accelerated repopulation of the tumor typically begins a few weeks after the start of a radiation treatment. If all the radiation can be crammed in before that time, the risks of tumor repopulation can be considerably reduced. In fact even external-beam radiotherapy is moving in this direction, with the use of highly accelerated protocols. The advantages of low dose rate stem from the differential response to fractionation of early- and late-responding tissues. Essentially, lowering the dose rate spares late-responding tissue more than it does early-responding tissue such as tumors. We shall also discuss some recent innovations in the context of the general principles that have been outlined. For example, High dose rate brachytherapy, particularly for the uterine cervix: Does it work? If so, when and why? Use of Ir-192 sources, with a half life of 70 days: Should corrections be made for changing biological effectiveness as the dose

Treatment planning for heavy ion radiotherapy: calculation and optimization of biologically effective dose

International Nuclear Information System (INIS)

Kraemer, M.; Scholz, M.

2000-09-01

We describe a novel approach to treatment planning for heavy ion radiotherapy based on the local effect model (LEM) which allows to calculate the biologically effective dose not only for the target region but for the entire irradiation volume. LEM is ideally suited to be used as an integral part of treatment planning code systems for active dose shaping devices like the GSI raster scan system. Thus, it has been incorporated into our standard treatment planning system for ion therapy (TRiP). Single intensity modulated fields can be optimized with respect to homogeneous biologically effective dose. The relative biological effectiveness (RBE) is calculated separately for each voxel of the patient CT. Our radiobiologically oriented code system is in use since 1995 for the planning of irradiation experiments with cell cultures and animals such as rats and minipigs. Since 1997 it is in regular and successful use for patient treatment planning. (orig.)

Biological dosimetry: chromosomal aberration analysis for dose assessment

International Nuclear Information System (INIS)

1986-01-01

In view of the growing importance of chromosomal aberration analysis as a biological dosimeter, the present report provides a concise summary of the scientific background of the subject and a comprehensive source of information at the technical level. After a review of the basic principles of radiation dosimetry and radiation biology basic information on the biology of lymphocytes, the structure of chromosomes and the classification of chromosomal aberrations are presented. This is followed by a presentation of techniques for collecting blood, storing, transporting, culturing, making chromosomal preparations and scaring of aberrations. The physical and statistical parameters involved in dose assessment are discussed and examples of actual dose assessments taken from the scientific literature are given

The biological bases of the dose-effect relationship

International Nuclear Information System (INIS)

Lafuma, J.

2001-01-01

In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

The biological effects of low doses of radiation: medical, biological and ecological aspects

International Nuclear Information System (INIS)

Gun-Aajav, T.; Ajnai, L.; Manlaijav, G.

2007-01-01

Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

SU-C-202-04: Adapting Biologically Optimized Dose Escalation Based On Mid-Treatment PET/CT for Non-Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Zhang, P; Kuo, L; Yorke, E; Hu, Y; Lockney, N; Mageras, G; Deasy, J; Rimner, A [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

2016-06-15

Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after the full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical

Radiation research contracts: Biological effects of small radiation doses

Energy Technology Data Exchange (ETDEWEB)

Hug, O [International Atomic Energy Agency, Division of Health, Safety and Waste Disposal, Vienna (Austria)

1959-04-15

To establish the maximum permissible radiation doses for occupational and other kinds of radiation exposure, it is necessary to know those biological effects which can be produced by very small radiation doses. This particular field of radiation biology has not yet been sufficiently explored. This holds true for possible delayed damage after occupational radiation exposure over a period of many years as well as for acute reactions of the organism to single low level exposures. We know that irradiation of less than 25 Roentgen units (r) is unlikely to produce symptoms of radiation sickness. We have, however, found indications that even smaller doses may produce certain instantaneous reactions which must not be neglected

Biological dose estimation and comet analysis of the victims in a high dose 60Co radiation accident

International Nuclear Information System (INIS)

Chen Ying; Liu Xiulin; Luo Yisheng; Li You; Yao Bo

2007-01-01

Objective: To explore the methods of chromosome preparation in human peripheral blood and bone marrow after very high dose exposure and fit the dose-response curve of dicentrics and tings in the range of high doses over 6 Gy for estimating biological dose and detecting DNA damage in the victims of '10.21' accident. Methods: The samples of peripheral blood and bone marrow in 2 victims were collected to prepare chromosome mataphases and dicentrics (multicentrics) + rings were counted. The dose-response curve and equation of human blood irradiated between 6-22 Gy in vitro were established and applied to assess biological dose of 2 victims. In addition, their DNA damages were tested by alkaline single cell gel electrophoresis. Results: The dicentric + ring numbers of 4.47 per cell in victims B's peripheral blood lymphocytes and 9.15 per cell in victim A's bone marrow who had no mitosis in peripheral blood cell. The whole body average doses of victims B and A estimated by 6-22 Gy equation arrived at 9.4 Gy and 19.5 Gy, respectively. The serious DNA damages were expressed by small head and large tail comet figures. Conclusions: The biological doses of 2 victims estimated by 6-22 Gy dose-response curve have reached the levels of extreme grave bone marrow and intestinal ARS, respectively. (authors)

Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

Directory of Open Access Journals (Sweden)

Y. Sobita Devi

2011-12-01

Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

The biological bases of the dose-effect relationship; Les bases biologiques de la relation dose-effet

Energy Technology Data Exchange (ETDEWEB)

Lafuma, J

2001-06-01

In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

Biological dose estimation for accidental supra-high dose gamma-ray exposure

International Nuclear Information System (INIS)

Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

2011-01-01

To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

Biological indicators for radiation absorbed dose: a review

International Nuclear Information System (INIS)

Paul, S.F.D.; Venkatachalam, P.; Jeevanram, R.K.

1996-01-01

Biological dosimetry has an important role to play in assessing the cumulative radiation exposure of persons working with radiation and also in estimating the true dose received during accidents involving external and internal exposure. Various biodosimetric methods have been tried to estimate radiation dose for the above purposes. Biodosimetric methods include cytogenetic, immunological and mutational assays. Each technique has certain advantages and disadvantages. We present here a review of each technique, the actual method used for detection of dose, the sensitivity of detection and its use in long term studies. (author)

A new method for dosing uranium in biological media

International Nuclear Information System (INIS)

Henry, Ph.; Kobisch, Ch.

1964-01-01

This report describes a new method for dosing uranium in biological media based on measurement of alpha activity. After treatment of the sample with a mineral acid, the uranium is reduced to the valency four by trivalent titanium and is precipitated as phosphate in acid solution. The uranium is then separated from the titanium by precipitation as UF 4 with lanthanum as carrier. A slight modification, unnecessary in the case of routine analyses, makes it possible to eliminate other possible alpha emitters (thorium and transuranic elements). (authors) [fr

Biological UV-doses and the effect on an ozone layer depletion

International Nuclear Information System (INIS)

Dahlback, A.; Henriksen, T.

1988-08-01

Effective UV-doses were calculated based on the integrated product of the biological action spectrum and the solar radiation. The calculations included absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. The effective annual UV-dose increases by approximately 4% per degree of latitude towards the equator. An ozone depletion of 1% increases the annual UV-dose by approximately 1% at 60 o N. A large depletion of 50% over Scandinavia (60 o N) would give this region an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 o N (California or the Mediterranean countries). The Antarctic ozone hole increases the annual UV-dose by 20 to 25% which is a similar increase as that attained by moving 5 to 6 degrees of latitude nearer the equator. The annual UV-dose on higher latitudes is mainly determined by the summer values of ozone. Both the ozone values and the effective UV-doses vary from one year to another (within ±4%). No positive or negative trend is observed for Scandinavia from 1978 to 1988

Imprecision in estimates of dose from ingested 137Cs due to variability in human biological characteristics

International Nuclear Information System (INIS)

Schwarz, G.; Dunning, D.E. Jr.

1982-01-01

An attempt has been made to quantify the variability in human biological parameters determining dose to man from ingestion of a unit activity of soluble 137 Cs and the resulting imprecision in the predicted total-body dose commitment. The analysis is based on an extensive review of the literature along with the application of statistical methods to determine parameter variability, correlations between parameters, and predictive imprecision. The variability in the principal biological parameters (biological half-time and total-body mass) involved can be described by a geometric standard deviation of 1.2-1.5 for adults and 1.6-1.9 for children/ adolescents of age 0.1-18 yr. The estimated predictive imprecision (using a Monte Carlo technique) in the total-body dose commitment from ingested 137 Cs can be described by a geometric standard deviation on the order of 1.3-1.4, meaning that the 99th percentile of the predicted distribution of dose is within approximately 2.1 times the mean value. The mean dose estimate is 0.009 Sv/MBq (34 mrem/μ Ci) for children/adolescents and 0.01 Sv/MBq (38 mrem/μ Ci) for adults. Little evidence of age dependence in the total-body dose from ingested 137 Cs is observed. (author)

Cytogenetic biological dosimetry. Dose estimative in accidental exposure

International Nuclear Information System (INIS)

Santos, O.R. dos; Campos, I.M.A. de.

1988-01-01

The methodology of cytogenetic biological dosimetry is studied. The application in estimation of dose in five cases of accidental exposure is reported. An hematological study and culture of lymphocytes is presented. (M.A.C.) [pt

Dose estimate of exposure to radioisotopes in molecular and cellular biology

International Nuclear Information System (INIS)

Onado, C.; Faretta, M.; Ubezio, P.

1999-01-01

A method for prospectively evaluating the annual equivalent doses and effective dose to biomedical researchers working with unsealed radioisotopes, and their classification, is presented here. Simplified formulae relate occupational data to a reasonable overestimate of the annual effective dose, and the equivalent doses to the hands and to the skin. The procedure, up to the classification of personnel and laboratories, can be made fully automatic, using a common spreadsheet on a personal computer. The method is based on occupational data, accounting for the amounts of each radioisotope used by a researcher, the time of exposure and the overall amounts employed in the laboratories where experiments are performed. The former data serve to forecast a contribution to the dose arising from a researcher's own work, the latter to a forecast of an 'environmental' contribution deriving simply from the presence in a laboratory where other people are working with radioisotopes. The estimates of the doses due to one's own radioisotope handling and to 'environment' were corrected for accidental exposure, considered as a linear function of the manipulated activity or of the time spent in the laboratories respectively, and summed up to give the effective dose. The effective dose associated with some common experiments in molecular and cellular biology is pre-evaluated by this method. (author)

TLD estimation of absorbed dose for 131I on the surface of biological organs of REMCAL phantom

International Nuclear Information System (INIS)

Tandon, Pankaj; Gaur, P.K.; Bhatt, B.C.; Soni, P.S.

2001-01-01

In nuclear medicine, the accuracy of absorbed dose of an internally distributed radiopharmaceuticals estimated by the MIRD (medical internal radiation dose) method depends on the cumulated activity of the source organs and their mass. The usual method for obtaining the cumulated activities are: 1) direct measurements by a) positron emission tomography (PET) and b) single photon emission computed tomography (SPECT) 2) extrapolation from animal data and 3) calculations based on the mathematical biokinetic model. Among these methods, extrapolation of animal data to humans includes inevitable inaccuracy due to large interspecies metabolic differences with regard to the administered radiochemical. Biokinetic modeling requires adequate knowledge of various kinetic parameters, which is based on some biological assumptions. Direct measurements can provide cumulated distributions with fewer biological assumptions. But direct measurements of PET/SPECT are difficult to perform routinely. A method has been developed to obtain the surface dose of different biological organs by using TLDs. Here, a number of TLDs are placed just above the surface of the biological organs of the REMCAL Alderson human phantom filled with water. Firstly, investigation of the accuracy of this method by calibration studies using the said phantom, which is having the entire biological organ intact and simulate the organs as human body is done. These organs are filled with the known activity of the radioisotope. In the present study, estimation of radiation dose received by fifteen different target organs, when the known activity was filled in the three major organs of interest was carried out

Dose rate effect models for biological reaction to ionizing radiation in human cell lines

International Nuclear Information System (INIS)

Magae, Junji; Ogata, Hiromitsu

2008-01-01

, suggesting that dose rate effect predicted by MOE model is dependent on DNA repair system. Dose rate effect in a resting normal fibroblast cultured in serum-depleted medium also followed MOE model. In contrast, dose-rate effect was observed in these cell lines deficient of DNA repair system, when they were cultured for more than several month. This dose rate effect did not fit MOE model, and followed a model based on elimination of damaged cells. In conclusion, dose rate effect in growth inhibition and micronucleus formation in cultured cell lines is dependent on dose rate and irradiation time: In higher range of dose rates and short irradiation time, biological effect is determined by dose but not dose rate, and dose rate effect is not observed. In middle range of dose rates and irradiation time, dose rate effect is dependent on DNA repair system, and follows MOE model. In low range of dose-rates and irradiation time longer than several months, dose rate effect is mainly dependent on elimination of damaged cells, and biological effect is determined by dose rate rather than total dose. Our results suggest that dose rate and irradiation time should be included in estimation of long-term radiation risk at low dose rates. (author)

Predicted allowable doses to normal organs for biologically targeted radiotherapy

International Nuclear Information System (INIS)

O'Donoghue, J.A.; Wheldon, T.E.; Western Regional Hospital Board, Glasgow

1988-01-01

The authors have used Dale's extension to the ''linear quadratic'' (LQ) model (Dale, 1985) to evaluate ''equivalent doses'' in cases involving exponentially decaying dose rates. This analysis indicates that the dose-rate effect will be a significant determinant of allowable doses to organs such as liver, kidney and lung. These organ tolerance doses constitute independent constraints on the therapeutic intensity of biologically targeted radiotherapy in exactly the same way as for conventional external beam radiotherapy. In the context of marrow rescue they will in all likelihood constitute the dose-limiting side-effects and thus be especially important. (author)

Quantitative global sensitivity analysis of a biologically based dose-response pregnancy model for the thyroid endocrine system.

Science.gov (United States)

Lumen, Annie; McNally, Kevin; George, Nysia; Fisher, Jeffrey W; Loizou, George D

2015-01-01

A deterministic biologically based dose-response model for the thyroidal system in a near-term pregnant woman and the fetus was recently developed to evaluate quantitatively thyroid hormone perturbations. The current work focuses on conducting a quantitative global sensitivity analysis on this complex model to identify and characterize the sources and contributions of uncertainties in the predicted model output. The workflow and methodologies suitable for computationally expensive models, such as the Morris screening method and Gaussian Emulation processes, were used for the implementation of the global sensitivity analysis. Sensitivity indices, such as main, total and interaction effects, were computed for a screened set of the total thyroidal system descriptive model input parameters. Furthermore, a narrower sub-set of the most influential parameters affecting the model output of maternal thyroid hormone levels were identified in addition to the characterization of their overall and pair-wise parameter interaction quotients. The characteristic trends of influence in model output for each of these individual model input parameters over their plausible ranges were elucidated using Gaussian Emulation processes. Through global sensitivity analysis we have gained a better understanding of the model behavior and performance beyond the domains of observation by the simultaneous variation in model inputs over their range of plausible uncertainties. The sensitivity analysis helped identify parameters that determine the driving mechanisms of the maternal and fetal iodide kinetics, thyroid function and their interactions, and contributed to an improved understanding of the system modeled. We have thus demonstrated the use and application of global sensitivity analysis for a biologically based dose-response model for sensitive life-stages such as pregnancy that provides richer information on the model and the thyroidal system modeled compared to local sensitivity analysis.

Quantitative global sensitivity analysis of a biologically based dose-response pregnancy model for the thyroid endocrine system

Directory of Open Access Journals (Sweden)

Annie eLumen

2015-05-01

Full Text Available A deterministic biologically based dose-response model for the thyroidal system in a near-term pregnant woman and the fetus was recently developed to evaluate quantitatively thyroid hormone perturbations. The current work focuses on conducting a quantitative global sensitivity analysis on this complex model to identify and characterize the sources and contributions of uncertainties in the predicted model output. The workflow and methodologies suitable for computationally expensive models, such as the Morris screening method and Gaussian Emulation processes, were used for the implementation of the global sensitivity analysis. Sensitivity indices, such as main, total and interaction effects, were computed for a screened set of the total thyroidal system descriptive model input parameters. Furthermore, a narrower sub-set of the most influential parameters affecting the model output of maternal thyroid hormone levels were identified in addition to the characterization of their overall and pair-wise parameter interaction quotients. The characteristic trends of influence in model output for each of these individual model input parameters over their plausible ranges were elucidated using Gaussian Emulation processes. Through global sensitivity analysis we have gained a better understanding of the model behavior and performance beyond the domains of observation by the simultaneous variation in model inputs over their range of plausible uncertainties. The sensitivity analysis helped identify parameters that determine the driving mechanisms of the maternal and fetal iodide kinetics, thyroid function and their interactions, and contributed to an improved understanding of the system modeled. We have thus demonstrated the use and application of global sensitivity analysis for a biologically based dose-response model for sensitive life-stages such as pregnancy that provides richer information on the model and the thyroidal system modeled compared to local

Biological effects of low doses of ionizing radiation

International Nuclear Information System (INIS)

Gonzalez, A.J.

1994-01-01

Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

Biological effects of low-dose ionizing radiation exposure; Biologische Wirkungen niedriger Dosen ionisierender Strahlung

Energy Technology Data Exchange (ETDEWEB)

Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst (comps.)

2009-07-01

The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

Physics must join with biology in better assessing risk from low-dose irradiation

International Nuclear Information System (INIS)

Feinendegen, L. E.; Neumann, R. D.

2005-01-01

This review summarises the complex response of mammalian cells and tissues to low doses of ionising radiation. This thesis encompasses induction of DNA damage, and adaptive protection against both renewed damage and against propagation of damage from the basic level of biological organisation to the clinical expression of detriment. The induction of DNA damage at low radiation doses apparently is proportional to absorbed dose at the physical/chemical level. However, any propagation of such damage to higher levels of biological organisation inherently follows a sigmoid function. Moreover, low-dose-induced inhibition of damage propagation is not linear, but instead follows a dose-effect function typical for adaptive protection, after an initial rapid rise it disappears at doses higher than ∼0.1-0.2 Gy to cells. The particular biological response duality at low radiation doses precludes the validity of the linear-no-threshold hypothesis in the attempt to relate absorbed dose to cancer. In fact, theory and observation support not only a lower cancer incidence than expected from the linear-no-threshold hypothesis, but also a reduction of spontaneously occurring cancer, a hormetic response, in the healthy individual. (authors)

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Energy Technology Data Exchange (ETDEWEB)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

International Nuclear Information System (INIS)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

Science.gov (United States)

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

Biological Bases for Radiation Adaptive Responses in the Lung

Energy Technology Data Exchange (ETDEWEB)

Scott, Bobby R. [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Lin, Yong [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Wilder, Julie [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Belinsky, Steven [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States)

2015-03-01

Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry

International Nuclear Information System (INIS)

Baechler, Sebastien; Hobbs, Robert F.; Prideaux, Andrew R.; Wahl, Richard L.; Sgouros, George

2008-01-01

In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial

The biologically equivalent dose BED - Is the approach for calculation of this factor really a reliable basis?

International Nuclear Information System (INIS)

Jensen, J.M.; Zimmermann, J.

2000-01-01

To predict the effect on tumours in radiotherapy, especially relating to irreversible effects, but also to realize the retrospective assessment the so called L-Q-model is relied on at present. Internal specific organ parameters, such as α, β, γ, T p , T k , and ρ, as well as external parameters, so as D, d, n, V, and V ref , were used for determination of the biologically equivalent dose BED. While the external parameters are determinable with small deviations, the internal parameters depend on biological varieties and dispersons: In some cases the lowest value is assumed to be Δ=±25%. This margin of error goes on to the biologically equivalent dose by means of the principle of superposition of errors. In some selected cases (lung, kidney, skin, rectum) these margins of error were calculated exemplarily. The input errors especially of the internal parameters cause a mean error Δ on the biologically equivalent dose and a dispersion of the single fraction dose d dependent on the organ taking into consideration, of approximately 8-30%. Hence it follows only a very critical and cautious application of those L-Q-algorithms in expert proceedings, and in radiotherapy more experienced based decisions are recommended, instead of acting only upon simple two-dimensional mechanistic ideas. (orig.) [de

Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

Directory of Open Access Journals (Sweden)

Elizabeth A Brezinski

Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

Low dose irradiation and biological defense mechanisms

International Nuclear Information System (INIS)

Sugahara, Tsutomu; Sagan, L.A.; Aoyama, Takashi

1992-01-01

It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

Dose painting based on tumor uptake of Cu-ATSM and FDG

DEFF Research Database (Denmark)

Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

2014-01-01

definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting...

Major cost savings associated with biologic dose reduction in patients with inflammatory arthritis.

LENUS (Irish Health Repository)

Murphy, C L

2015-01-01

The purpose of this study was to explore whether patients with Inflammatory Arthritis (IA) (Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Ankylosing Spondylitis (AS)) would remain in remission following a reduction in biologic dosing frequency and to calculate the cost savings associated with dose reduction. This prospective non-blinded non-randomised study commenced in 2010. Patients with Inflammatory Arthritis being treated with a biologic agent were screened for disease activity. A cohort of those in remission according to standardized disease activity indices (DAS28 < 2.6, BASDAI < 4) was offered a reduction in dosing frequency of two commonly used biologic therapies (etanercept 50 mg once per fortnight instead of weekly, adalimumab 40 mg once per month instead of fortnightly). Patients were assessed for disease activity at 3, 6, 12, 18 and 24 months following reduction in dosing frequency. Cost saving was calculated. 79 patients with inflammatory arthritis in remission were recruited. 57% had rheumatoid arthritis (n = 45), 13% psoriatic arthritis (n = 10) and 30% ankylosing spondylitis (n = 24). 57% (n = 45) were taking etanercept and 43% (n = 34) adalimumab. The percentage of patients in remission at 24 months was 56% (n = 44). This resulted in an actual saving to the state of approximately 600,000 euro over two years. This study demonstrates the reduction in biologic dosing frequency is feasible in Inflammatory Arthritis. There was a considerable cost saving at two years. The potential for major cost savings in biologic usage should be pursued further.

Biological monitoring to determine worker dose in a butadiene processing plant

Energy Technology Data Exchange (ETDEWEB)

Bechtold, W.E.; Hayes, R.B. [National Cancer Inst., Bethesda, MD (United States)

1995-12-01

Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to better assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Flickinger, J C; Kalend, A [Pittsburgh University School of Medicine (USA). Department of Radiation Oncology Pittsburg Cancer Institute (USA)

1990-03-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

International Nuclear Information System (INIS)

Flickinger, J.C.; Kalend, A.

1990-01-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

2009-01-01

High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

Dose estimation by biological methods; Estimacion de dosis por metodos biologicos

Energy Technology Data Exchange (ETDEWEB)

Guerrero C, C; David C, L; Serment G, J; Brena V, M [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

1997-07-01

The human being is exposed to strong artificial radiation sources, mainly of two forms: the first is referred to the occupationally exposed personnel (POE) and the second, to the persons that require radiological treatment. A third form less common is by accidents. In all these conditions it is very important to estimate the absorbed dose. The classical biological dosimetry is based in the dicentric analysis. The present work is part of researches to the process to validate the In situ Fluorescent hybridation (FISH) technique which allows to analyse the aberrations on the chromosomes. (Author)

Definition of the dose(tempo)-distribution in the biological irradiation-facility of the RIVM

International Nuclear Information System (INIS)

Bader, F.J.M.

1990-02-01

The RIVM biological irradiation facility (BBF) for the irradiation of biological samples and small animals is a self shielded device and can be safely operated in an existing laboratory environment. There are two 137 Cs sources (15TBq) in a bilateral geometry to give maximum dose uniformity. The easily accessible irradiation chamber is housed in a rotating lead shielding. The dosimetry of BBF was performed by the Dosimetry Section of the RIVM. Experiments were made to determine the absorbed dose in plastic tubes filled with water and the dose distribution over the tube-holder. Separate experiments were made to determine the absorbed dose during the rotation of the irradiation chamber and to check the irradiation timer. For the experiments LiF:Mg,Ti (TLD-100) extruded ribbons were used. The TLDs were calibrated in a collimated beam of 137 Cs gamma rays. The determination of the absorbed dose in water was based on a users biological irradiation set up. The TLDs were individually sealed in thin plastic foil and put in plastic tubes filled for 1/3 with water. The tubes were vertically placed in the tube-holder and placed in the centre of the irradiation chamber. The results show that the absorbed dose in water (determined on January 1, 1990) is equal to 0.97 Gy/timer-unit, with a total uncertainty of 7 percent (1σ). During the rotation of the irradiation chamber the absorbed dose (determined on January 1, 1990) is equal to 0.38 Gy, with a total uncertainty of 15 percent (1σ). The variation of the dose distribution was determined at 15 different measurement points distributed over the tube-holder. The dosis in the measurement point in the centre of the tube-holder was taken as reference value. The maximum observed deviation over the other 14 measurement points amounts to -16 percent of it. The BBF-timer was checked against a special timer. The results indicate that within a range from 2-11 'timer-units' no differences are present. (author). 6 refs.; 6 figs.; 3 fotos

Biological-based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy

International Nuclear Information System (INIS)

Diot, Quentin; Kavanagh, Brian; Timmerman, Robert; Miften, Moyed

2012-01-01

Purpose: To describe biological-based optimization and Monte Carlo (MC) dose calculation-based treatment planning for volumetric modulated arc therapy (VMAT) delivery of stereotactic body radiation therapy (SBRT) in lung, liver, and prostate patients. Methods: Optimization strategies and VMAT planning parameters using a biological-based optimization MC planning system were analyzed for 24 SBRT patients. Patients received a median dose of 45 Gy [range, 34-54 Gy] for lung tumors in 1-5 fxs and a median dose of 52 Gy [range, 48-60 Gy] for liver tumors in 3-6 fxs. Prostate patients received a fractional dose of 10 Gy in 5 fxs. Biological-cost functions were used for plan optimization, and its dosimetric quality was evaluated using the conformity index (CI), the conformation number (CN), the ratio of the volume receiving 50% of the prescription dose over the planning target volume (Rx/PTV50). The quality and efficiency of the delivery were assessed according to measured quality assurance (QA) passing rates and delivery times. For each disease site, one patient was replanned using physical cost function and compared to the corresponding biological plan. Results: Median CI, CN, and Rx/PTV50 for all 24 patients were 1.13 (1.02-1.28), 0.79 (0.70-0.88), and 5.3 (3.1-10.8), respectively. The median delivery rate for all patients was 410 MU/min with a maximum possible rate of 480 MU/min (85%). Median QA passing rate was 96.7%, and it did not significantly vary with the tumor site. Conclusions: VMAT delivery of SBRT plans optimized using biological-motivated cost-functions result in highly conformal dose distributions. Plans offer shorter treatment-time benefits and provide efficient dose delivery without compromising the plan conformity for tumors in the prostate, lung, and liver, thereby improving patient comfort and clinical throughput. The short delivery times minimize the risk of patient setup and intrafraction motion errors often associated with long SBRT treatment

The use of biologically based cancer risk models in radiation epidemiology

International Nuclear Information System (INIS)

Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

2003-01-01

Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies

CERN Document Server

Wambersie, A; Menzel, H G; Gahbauer, R; DeLuca, P M; Hendry, J H; Jones, D T L

2011-01-01

When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatment prescription. However, the clinical outcome does not only depend on absorbed dose but also on a number of other factors such as dose per fraction, overall treatment time and radiation quality radiation biology effectiveness (RBE). Therefore, weighting factors have to be applied when different types of treatments are to be compared or to be combined. This had led to the concept of `isoeffective absorbed dose', introduced by ICRU and International Atomic Energy Agency (IAEA). The isoeffective dose D(IsoE) is the dose of a treatment carried out under reference conditions producing the same clinical effects on the target volume as those of the actual treatment. It i...

Biological evidence of low ionizing radiation doses; Biologischer Nachweis niedriger Dosen ionisierender Strahlung

Energy Technology Data Exchange (ETDEWEB)

Mirsch, Johanna

2017-03-17

Throughout life, every person is constantly exposed to different types of ionising radiation, without even noticing the exposure. The mean radiation exposure for people living in Germany amounts to approximately 4 mSv per year and encompasses the exposure from natural and man-made sources. The risks associated with exposure to low doses of radiation are still the subject of intense and highly controversial discussions, emphasizing the social relevance of studies investigating the effects of low radiation doses. In this thesis, DNA double-strand breaks (DSBs) were analyzed within three projects covering different aspects. DSBs are among the most hazardous DNA lesions induced by ionizing radiation, because this type of damage can easily lead to the loss of genetic information. Consequently, the DSB presents a high risk for the genetic integrity of the cell. In the first project, extensive results uncovered the track structure of charged particles in a biological model tissue. This provided the first biological data that could be used for comparison with data that were measured or predicted using theoretical physical dosimetry methods and mathematical simulations. Charged particles contribute significantly to the natural radiation exposure and are used increasingly in cancer radiotherapy because they are more efficient in tumor cell killing than X- or γ-rays. The difference in the biological effects of high energy charged particles compared with X- or γ-rays is largely determined by the spatial distribution of their energy deposition and the track structure inducing a three-dimensional damage pattern in living cells. This damage pattern consists of cells directly hit by the particle receiving a high dose and neighboring cells not directly hit by primary particles but exposed to far-reaching secondary electrons (δ-electrons). These cells receive a much lower dose deposition in the order of a few mGy. The radial dose distribution of single particle tracks was

Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response

International Nuclear Information System (INIS)

Oliveira, Romero Marcilio Barros Matias de

2002-08-01

Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1- -4 + (1,24 ±0,62) x 10 -2 D + (5,67 ± 0,64) x 10 -2 D 2 . (author)

Biological effects of low doses of radiation at low dose rate

International Nuclear Information System (INIS)

1996-05-01

The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

On the sensitivity of IMRT dose optimization to the mathematical form of a biological imaging-based prescription function

International Nuclear Information System (INIS)

Bowen, Stephen R; Bentzen, Soeren M; Jeraj, Robert; Flynn, Ryan T

2009-01-01

Voxel-based prescriptions of deliberately non-uniform dose distributions based on molecular imaging, so-called dose painting or theragnostic radiation therapy, require specification of a transformation that maps the image data intensities to prescribed doses. However, the functional form of this transformation is currently unknown. An investigation into the sensitivity of optimized dose distributions resulting from several possible prescription functions was conducted. Transformations between the radiotracer activity concentrations from Cu-ATSM PET images, as a surrogate of tumour hypoxia, and dose prescriptions were implemented to yield weighted distributions of prescribed dose boosts in high uptake regions. Dose escalation was constrained to reflect clinically realistic whole tumour doses and constant normal tissue doses. Optimized heterogeneous dose distributions were found by minimizing a voxel-by-voxel quadratic objective function in which all tumour voxels were given equal weight. Prescriptions based on a polynomial mapping function were found to be least constraining on their optimized plans, while prescriptions based on a sigmoid mapping function were the most demanding to deliver. A prescription formalism that fixed integral dose was less sensitive to errors in the choice of the mapping function than one that boosted integral dose. Integral doses to normal tissue and critical structures were insensitive to the shape of the prescription function. Planned target dose conformity improved with smaller beamlet dimensions until the inherent spatial resolution of the functional image was matched. Clinical implementation of dose painting depends on advances in absolute quantification of functional images and improvements in delivery techniques over smaller spatial scales.

Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure, and genetic sensitivity to neoplastic transformation

International Nuclear Information System (INIS)

Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

1978-01-01

A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure, and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6, and 15 months) were given five doses (20, 60, 180, 540, and 1620 rad) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rad/day and 25 rad/min). Forty to sixty mice were used in each of the approximately 110 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replication. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the 15-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used

Gamma-irradiated onions as a biological indicator of radiation dose

International Nuclear Information System (INIS)

Vaijapurkar, S.G.; Agarwal, Deepshikha; Chaudhuri, S.K.; Ram Senwar, Kana; Bhatnagar, P.K.

2001-01-01

Post-irradiation identification and dose estimation are required to assess the radiation-induced effects on living things in any nuclear emergency. In this study, radiation-induced morphological/cytological changes i.e., number of root formation and its length, shooting length, reduction in mitotic index, micronuclei formation and chromosomal aberrations in the root tip cells of gamma-irradiated onions at lower doses (50-2000 cGy) are reported. The capabilities of this biological species to store the radiation-induced information are also studied

TU-AB-BRC-02: Accuracy Evaluation of GPU-Based OpenCL Carbon Monte Carlo Package (goCMC) in Biological Dose and Microdosimetry in Comparison to FLUKA Simulations

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Peeler, C; Qin, N; Jiang, S; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: One of the most accurate methods for radiation transport is Monte Carlo (MC) simulation. Long computation time prevents its wide applications in clinic. We have recently developed a fast MC code for carbon ion therapy called GPU-based OpenCL Carbon Monte Carlo (goCMC) and its accuracy in physical dose has been established. Since radiobiology is an indispensible aspect of carbon ion therapy, this study evaluates accuracy of goCMC in biological dose and microdosimetry by benchmarking it with FLUKA. Methods: We performed simulations of a carbon pencil beam with 150, 300 and 450 MeV/u in a homogeneous water phantom using goCMC and FLUKA. Dose and energy spectra for primary and secondary ions on the central beam axis were recorded. Repair-misrepair-fixation model was employed to calculate Relative Biological Effectiveness (RBE). Monte Carlo Damage Simulation (MCDS) tool was used to calculate microdosimetry parameters. Results: Physical dose differences on the central axis were <1.6% of the maximum value. Before the Bragg peak, differences in RBE and RBE-weighted dose were <2% and <1%. At the Bragg peak, the differences were 12.5% caused by small range discrepancy and sensitivity of RBE to beam spectra. Consequently, RBE-weighted dose difference was 11%. Beyond the peak, RBE differences were <20% and primarily caused by differences in the Helium-4 spectrum. However, the RBE-weighted dose agreed within 1% due to the low physical dose. Differences in microdosimetric quantities were small except at the Bragg peak. The simulation time per source particle with FLUKA was 0.08 sec, while goCMC was approximately 1000 times faster. Conclusion: Physical doses computed by FLUKA and goCMC were in good agreement. Although relatively large RBE differences were observed at and beyond the Bragg peak, the RBE-weighted dose differences were considered to be acceptable.

Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

Energy Technology Data Exchange (ETDEWEB)

Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

1987-01-01

Biological clearance half-lives (Tsub(b)) of different /sup 99/Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values.

Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

International Nuclear Information System (INIS)

Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

1987-01-01

Biological clearance half-lives (Tsub(b)) of different 99 Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values. (author)

Biological profiling and dose-response modeling tools ...

Science.gov (United States)

Through its ToxCast project, the U.S. EPA has developed a battery of in vitro high throughput screening (HTS) assays designed to assess the potential toxicity of environmental chemicals. At present, over 1800 chemicals have been tested in up to 600 assays, yielding a large number of concentration-response data sets. Standard processing of these data sets involves finding a best fitting mathematical model and set of model parameters that specify this model. The model parameters include quantities such as the half-maximal activity concentration (or “AC50”) that have biological significance and can be used to inform the efficacy or potency of a given chemical with respect to a given assay. All of this data is processed and stored in an online-accessible database and website: http://actor.epa.gov/dashboard2. Results from these in vitro assays are used in a multitude of ways. New pathways and targets can be identified and incorporated into new or existing adverse outcome pathways (AOPs). Pharmacokinetic models such as those implemented EPA’s HTTK R package can be used to translate an in vitro concentration into an in vivo dose; i.e., one can predict the oral equivalent dose that might be expected to activate a specific biological pathway. Such predicted values can then be compared with estimated actual human exposures prioritize chemicals for further testing.Any quantitative examination should be accompanied by estimation of uncertainty. We are developing met

TU-AB-BRC-09: Fast Dose-Averaged LET and Biological Dose Calculations for Proton Therapy Using Graphics Cards

International Nuclear Information System (INIS)

Wan, H; Tseung, Chan; Beltran, C

2016-01-01

Purpose: To demonstrate fast and accurate Monte Carlo (MC) calculations of proton dose-averaged linear energy transfer (LETd) and biological dose (BD) on a Graphics Processing Unit (GPU) card. Methods: A previously validated GPU-based MC simulation of proton transport was used to rapidly generate LETd distributions for proton treatment plans. Since this MC handles proton-nuclei interactions on an event-by-event using a Bertini intranuclear cascade-evaporation model, secondary protons were taken into account. The smaller contributions of secondary neutrons and recoil nuclei were ignored. Recent work has shown that LETd values are sensitive to the scoring method. The GPU-based LETd calculations were verified by comparing with a TOPAS custom scorer that uses tabulated stopping powers, following recommendations by other authors. Comparisons were made for prostate and head-and-neck patients. A python script is used to convert the MC-generated LETd distributions to BD using a variety of published linear quadratic models, and to export the BD in DICOM format for subsequent evaluation. Results: Very good agreement is obtained between TOPAS and our GPU MC. Given a complex head-and-neck plan with 1 mm voxel spacing, the physical dose, LETd and BD calculations for 10"8 proton histories can be completed in ∼5 minutes using a NVIDIA Titan X card. The rapid turnover means that MC feedback can be obtained on dosimetric plan accuracy as well as BD hotspot locations, particularly in regards to their proximity to critical structures. In our institution the GPU MC-generated dose, LETd and BD maps are used to assess plan quality for all patients undergoing treatment. Conclusion: Fast and accurate MC-based LETd calculations can be performed on the GPU. The resulting BD maps provide valuable feedback during treatment plan review. Partially funded by Varian Medical Systems.

TU-AB-BRC-09: Fast Dose-Averaged LET and Biological Dose Calculations for Proton Therapy Using Graphics Cards

Energy Technology Data Exchange (ETDEWEB)

Wan, H; Tseung, Chan; Beltran, C [Mayo Clinic, Rochester, MN (United States)

2016-06-15

Purpose: To demonstrate fast and accurate Monte Carlo (MC) calculations of proton dose-averaged linear energy transfer (LETd) and biological dose (BD) on a Graphics Processing Unit (GPU) card. Methods: A previously validated GPU-based MC simulation of proton transport was used to rapidly generate LETd distributions for proton treatment plans. Since this MC handles proton-nuclei interactions on an event-by-event using a Bertini intranuclear cascade-evaporation model, secondary protons were taken into account. The smaller contributions of secondary neutrons and recoil nuclei were ignored. Recent work has shown that LETd values are sensitive to the scoring method. The GPU-based LETd calculations were verified by comparing with a TOPAS custom scorer that uses tabulated stopping powers, following recommendations by other authors. Comparisons were made for prostate and head-and-neck patients. A python script is used to convert the MC-generated LETd distributions to BD using a variety of published linear quadratic models, and to export the BD in DICOM format for subsequent evaluation. Results: Very good agreement is obtained between TOPAS and our GPU MC. Given a complex head-and-neck plan with 1 mm voxel spacing, the physical dose, LETd and BD calculations for 10{sup 8} proton histories can be completed in ∼5 minutes using a NVIDIA Titan X card. The rapid turnover means that MC feedback can be obtained on dosimetric plan accuracy as well as BD hotspot locations, particularly in regards to their proximity to critical structures. In our institution the GPU MC-generated dose, LETd and BD maps are used to assess plan quality for all patients undergoing treatment. Conclusion: Fast and accurate MC-based LETd calculations can be performed on the GPU. The resulting BD maps provide valuable feedback during treatment plan review. Partially funded by Varian Medical Systems.

EUD-based biological optimization for carbon ion therapy

International Nuclear Information System (INIS)

Brüningk, Sarah C.; Kamp, Florian; Wilkens, Jan J.

2015-01-01

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

Clinical oncology based upon radiation biology

International Nuclear Information System (INIS)

Hirata, Hideki

2016-01-01

This paper discussed the biological effects of radiation as physical energy, especially those of X-ray as electromagnetic radiation, by associating the position of clinical oncology with classical radiation cell biology as well as recent molecular biology. First, it described the physical and biological effects of radiation, cell death due to radiation and recovery, radiation effects at tissue level, and location information and dosage information in the radiotherapy of cancer. It also described the territories unresolved through radiation biology, such as low-dose high-sensitivity, bystander effects, etc. (A.O.)

The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

Science.gov (United States)

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

International Nuclear Information System (INIS)

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

Low doses of ionizing radiation: Biological effects and regulatory control. Invited papers and discussions. Proceedings of an international conference

International Nuclear Information System (INIS)

1998-01-01

The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference

Evaluation of experimental animal biological state at exposure to low-dose ionizing radiation

International Nuclear Information System (INIS)

Rozanov, V.A.; Rejtarova, T.Je.; Chernyikov, G.B.; Timoshevs'ka, Je.V.; Kozozojeva, O.O.

1997-01-01

New approaches to quantitative evaluation of ionizing radiation absorbed dose within the low-dose range (up to 400 mGy) according to the degree of the organism biological response was developed. The purpose of the stage of the work published in Communication 1 is to evaluate the shifts in the animal behaviour and cellular composition of the blood at irradiation by the dose of 100,200 and 400 mGy. Distinct dose dependence of behaviour reactions and hematological indices within the dose range of 100-400 mGy was not noted

The choice of a biological model in assessing internal dose equivalent

International Nuclear Information System (INIS)

Parodo, A.; Erre, N.

1977-01-01

Many are the biological models related to kinetic behavior of radioactive materials within the organism, or in an organ. This is true particularly for the metabolic kinetics of bone-seekers radionuclides described differently by various authors: as a consequence, different forms of the retention function have been used in calculating internal dose equivalent. In our opinion, the retention functions expressed as linear combinations of exponential terms with negative exponents are preferable. In fact, they can be obtained by coherent compartmental analysis and allow a mathematical formalism fairly well definite and easily adaptable to computers. Moreover, it is possible to make use of graphs and monograms already published. The role of the biological model in internal dosimetry, referred to the reliability of the quantitative informations on the kinetic behavior of the radionuclides in the organism and, therefrom, to the accuracy of the doses calculated, is discussed. By comparing the results obtained with different biological models, one finds that the choice of a model is less important than the choice of the value of the appropriate parameters

Donor-specific cell-based assays in studying sensitivity to low-dose radiation: a population-based perspective

Directory of Open Access Journals (Sweden)

Dora eIl'yasova

2014-11-01

Full Text Available Currently, a linear no-threshold model is used to estimate health risks associated with exposure to low-dose radiation, a prevalent exposure in the general population, because the direct estimation from epidemiological studies suffers from uncertainty. This model has been criticized based on unique biology of low-dose radiation. Whether the departure from linearity is toward increased or decreased risk is intensely debated. We present an approach based on individual radiosensitivity testing and discuss how individual radiosensitivity can be assessed with the goal to develop a quantifiable measure of cellular response that can be conducted via high-throughput population testing.

Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.

Science.gov (United States)

Jones, Hannah M; Mayawala, Kapil; Poulin, Patrick

2013-04-01

Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.

Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

Science.gov (United States)

Ainsbury, Elizabeth A; Higueras, Manuel; Puig, Pedro; Einbeck, Jochen; Samaga, Daniel; Barquinero, Joan Francesc; Barrios, Lleonard; Brzozowska, Beata; Fattibene, Paola; Gregoire, Eric; Jaworska, Alicja; Lloyd, David; Oestreicher, Ursula; Romm, Horst; Rothkamm, Kai; Roy, Laurence; Sommer, Sylwester; Terzoudi, Georgia; Thierens, Hubert; Trompier, Francois; Vral, Anne; Woda, Clemens

2017-01-01

Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure and genetic sensitivity to neoplastic transformation

International Nuclear Information System (INIS)

Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

1978-01-01

A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6 and l5 months) were given five doses (20, 60, 180, 540, and 1620 rads) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rads/day and 25 rads/min). Forty to sixty mice were used in each of the approximately 119 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replicaton. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the l5-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used. It was also concluded that radiaton-induced neoplastic transformaton was significantly greater in mice with a known genetic sensitivity to neoplastic disease than in mammals which do not normally have a significant incidence of tumours. (author)

Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

International Nuclear Information System (INIS)

Ng, C.Y.P.; Kong, E.Y.; Konishi, T.; Kobayashi, A.; Suya, N.; Cheng, S.H.; Yu, K.N.

2015-01-01

The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis. - Highlights: • Neutron dose response was determined for embryos of the zebrafish, Danio rerio. • Neutron doses of 0.6, 1 and 2.5 mGy led to neutron hormetic effects. • Neutron doses of 70 and 100 mGy accompanied by gamma rays led to gamma-ray hormesis

The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy

International Nuclear Information System (INIS)

Clark, Brenda G.; Souhami, Luis; Pla, Conrado; Al-Amro, Abdullah S.; Bahary, Jean-Paul; Villemure, Jean-Guy; Caron, Jean-Louis; Olivier, Andre; Podgorsak, Ervin B.

1998-01-01

Purpose: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. Materials and Methods: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. Results: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. Conclusions: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue

Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs

International Nuclear Information System (INIS)

Ippolitov, Yu.A.; Kovtun, N.N.; Timofeev, L.V.

1999-01-01

Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs is studied. Obtained data illustrate the interactions between tissues in local exposure of live tissue to beta-radiation and determine the threshold total dose as 400 sGy. Higher doses lead to secondary changes in the gingival mucosa after which the tissue barrier does not recover [ru

Biological dose assessment of 15 victims in Haerbin radiation accident

International Nuclear Information System (INIS)

Liu, Jian-xiang; Huang, Min-yan; Ruan, Jian-lei; Bai, Yu-shu; Xu, Su

2008-01-01

Full text: a) On July 5 and 8, 2005, Two patients with bone marrow suppression were successively hospitalized by the First Affiliated Hospital of Haerbin Medical University. Examination results showed that the patients seemed to get suspicious radiation disease. On July 13, 2005, a radioactive source was found in the patients' dwelling. The radiation source is Iridium-192 with 0.5 Ci(1.85 x 10 10 Bq) radioactivity. The radiation source is a metal bar which is a kind of radioactive industrial detection source for welding. The source is currently stored in the urban radioactive waste storehouse of Heilongjiang province. After finding the radioactive source on July 13, The Haerbin municipal government initiated an emergency response plan and developed medical rescue, radioactive source examination and case detection through organizing ministries involving health, environmental protection and public security. After receiving a report at 17:00 on July 14, 2005, Chinese Ministry of Health immediately sent experts to the spot for investigation, dose estimation and direction of patients' rescue. Health authority carried out physical examination twice on 113 residents within 30 meters to the source, among which 4 got radiation sickness, 5 showed abnormal hemotogram, and others showed no abnormal response. Of 4 patients with radiation sickness, one 81 year old patient has died of severe bone marrow form of sub acute radiation sickness coupled with lung infection and prostrate apparatus at 13:00 on Oct., 20. Two children have been treated in Beitaiping Road Hospital in Beijing, another patient has been treated in local hospital. b) Biological dosimetry using conventional chromosome aberration analysis in human peripheral blood lymphocytes has been shown as a reliable and useful tool in medical management of radiation accident victims. Peripheral blood lymphocytes of the victims were cultured using conventional culture medium with colchicine added at the beginning. Chromosome

Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

International Nuclear Information System (INIS)

Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

2006-01-01

Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters (α=0.15 Gy -1 and α/β=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD 2 ) with respect to three effects: edema, RBE, and dose heterogeneity for 125 I and 103 Pd implants. The EUD 2 analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V 100 (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D 90 (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for 125 I and 103 Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for 125 I and 1.3-1.6 for 103 Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies

Dose inhomogeneities at various levels of biological organization

International Nuclear Information System (INIS)

Bond, V.P.

1988-01-01

Dose inhomogeneities in both tumor and normal tissue, inherent to the application of boron neutron capture therapy (BNCT), can be the result not only of ununiform distribution of 10 B at various levels of biological organization, but also of the distribution of the thermal neutrons and of the energy depositions from more energetic neutrons and other radiations comprising the externally-applied beams. The severity of the problems resulting from such inhomogeneities, and approaches to evaluating them, are illustrated by three examples, at the macro, micro and intermediate levels

Low dose effects of ionizing radiations in in vitro and in vivo biological systems: a multi-scale approach study

International Nuclear Information System (INIS)

Antoccia, A.; Berardinelli, F.; Argazzi, E.; Balata, M.; Bedogni, R.

2011-01-01

Long-term biological effects of low-dose radiation are little known nowadays and its carcinogenic risk is estimated on the assumption that risk remains linearly proportional to the radiation dose down to low-dose levels. However in the last 20 years this hypothesis has gradually begun to seem in contrast with a huge collection of experimental evidences, which has shown the presence of plethora of non-linear phenomena (including hypersensitivity and induced radioresistance, adaptive response, and non-targeted phenomena like bystander effect and genomic instability) occurring after low-dose irradiation. These phenomena might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the Linear No-Threshold (LNT) model currently used for cancer risk assessment through extrapolation from existing high-dose data. Moreover only few information is available regarding the effects induced on cryo preserved cells by multi-year background radiation exposure, which might induce a radiation-damage accumulation, due to the inhibition of cellular repair mechanisms. In this framework, the multi-year Excalibur (Exposure effects at low doses of ionizing radiation in biological culture) experiment, funded by INFN-CNS5, has undertaken a multi-scale approach investigation on the biological effects induced in in vitro and in vivo biological systems, in culture and cryo preserved conditions, as a function of radiation quality (X/γ-rays, protons, He-4 ions of various energies) and dose, with particular emphasis on the low-dose region and non-linear phenomena, in terms of different biological endpoints.

Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution

International Nuclear Information System (INIS)

Paganetti, H.

2005-01-01

Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological 'track structure' model and the more mechanistic 'lethal lesion/potentially lethal lesion' (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values

OEDIPE, a software for personalized Monte Carlo dosimetry and treatment planning optimization in nuclear medicine: absorbed dose and biologically effective dose considerations

International Nuclear Information System (INIS)

Petitguillaume, A.; Broggio, D.; Franck, D.; Desbree, A.; Bernardini, M.; Labriolle Vaylet, C. de

2014-01-01

For targeted radionuclide therapies, treatment planning usually consists of the administration of standard activities without accounting for the patient-specific activity distribution, pharmacokinetics and dosimetry to organs at risk. The OEDIPE software is a user-friendly interface which has an automation level suitable for performing personalized Monte Carlo 3D dosimetry for diagnostic and therapeutic radionuclide administrations. Mean absorbed doses to regions of interest (ROIs), isodose curves superimposed on a personalized anatomical model of the patient and dose-volume histograms can be extracted from the absorbed dose 3D distribution. Moreover, to account for the differences in radiosensitivity between tumoral and healthy tissues, additional functionalities have been implemented to calculate the 3D distribution of the biologically effective dose (BED), mean BEDs to ROIs, isoBED curves and BED-volume histograms along with the Equivalent Uniform Biologically Effective Dose (EUD) to ROIs. Finally, optimization tools are available for treatment planning optimization using either the absorbed dose or BED distributions. These tools enable one to calculate the maximal injectable activity which meets tolerance criteria to organs at risk for a chosen fractionation protocol. This paper describes the functionalities available in the latest version of the OEDIPE software to perform personalized Monte Carlo dosimetry and treatment planning optimization in targeted radionuclide therapies. (authors)

Fetal dose from radiotherapy photon beams: Physical basis, techniques to estimate radiation dose outside of the treatment field, biological effects and professional considerations

International Nuclear Information System (INIS)

Stovell, Marilyn; Blackwell, C. Robert

1997-01-01

Purpose/Objective: The presentation will review: 1. The physical basis of radiation dose outside of the treatment field. 2. Techniques to estimate and reduce fetal dose. 3. Clinical examples of fetal dose estimation and reduction. 4. Biological effects of fetal irradiation. 5. Professional considerations. Approximately 4000 women per year in the United States require radiotherapy during pregnancy. This report presents data and techniques that allow the medical physicist to estimate the radiation dose the fetus will receive and to reduce this dose with appropriate shielding. Out-of-beam data are presented for a variety of photon beams, including cobalt-60 gamma rays and x rays from 4 to 18 MV. Designs for simple and inexpensive to more complex and expensive types of shielding equipment are described. Clinical examples show that proper shielding can reduce the radiation dose to the fetus by 50%. In addition, a review of the biological aspects of irradiation enables estimates of the risks of lethality, growth retardation, mental retardation, malformation, sterility, cancer induction, and genetic defects to the fetus. A summary of professional considerations/recommendations is also provided as a guide for the radiation oncologist and medical physicist

Normal tissue dose-effect models in biological dose optimisation

International Nuclear Information System (INIS)

Alber, M.

2008-01-01

Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

International Nuclear Information System (INIS)

Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

2010-01-01

Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

Low doses of ionizing radiation: Relationship between biological benefit and damage induction. A synopsis

International Nuclear Information System (INIS)

Feinendegen, L.E.

2005-01-01

Absorption of ionizing radiation in biological tissue stochastically interacts with constituent atoms and molecules and always generates energy deposition (track) events accompanied by bursts of reactive oxygen species (ROS). These ROS are quite similar to those ROS that arise abundantly and constantly by normal oxidative metabolism. ROS effects from either source need attention when assessing radiation-induced alterations in biological structure and function. Endogenous ROS alone induce about 10 6 DNA oxyadducts per cell per day compared to about 5x10 -3 total DNA damage per average cell per day from background radiation exposure (1 mGy per year). At this background level, the corresponding ratio of probabilities of endogenous versus radiogenic DNA double strand breaks (DSBs) per cell per day is about 103 with some 25-40 % of low-LET caused radiogenic DNA-DSBs being of the multi-damage-site type. Radiogenic DNA damage increases in proportion to absorbed dose over a certain dose range. By evolution, tissues possess physiological mechanisms of protection against an array of potentially toxic agents, externally from the environment and endogenously from metabolism, mainly against the abundantly and constantly produced ROS. Ad hoc protection operates at a level that is genetically determined. Following small to moderate perturbation of cell-tissue homeostasis by a toxic impact, adaptive responses develop with a delay and may last from hours to weeks, even months, and aim at protecting the system against renewed insults. Protective responses encompass defense by scavenging mechanisms, DNA repair, damage removal largely by apoptosis and immune responses, as well as changes in cell proliferation. Acute low-dose irradiation below about 0.2 Gy can not only disturb cell-tissue homeostasis but also initiate adaptived protection that appears with a delay of hours and may last from less than a day to months. The balance between damage production and adaptive protection favors

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

International Nuclear Information System (INIS)

Calabrese, Edward J.; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.

2007-01-01

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines

Biological dose estimation in a radiation accident involving low-dose ...

African Journals Online (AJOL)

Blood specimens were collected from 8 people 18 days after they had been accidentally exposed to a 947,2 GBq iridium192 source during industrial application. The equivalent whole-body dose received at day 0 was estimated using a model based on quantitative and qualitative chromosome aberration analysis in ...

Assay of micronuclei in peripheral blood lymphocytes as a biological indicator of radiation dose

International Nuclear Information System (INIS)

Sreedevi, B.; Rao, B.S.

1994-01-01

Chromosomal aberration analysis (CA) has regularly been used as a biological dosemeter to evaluate suspected overexposures to ionising radiations. Recently, the micronucleus (MN) assay has been suggested as an alternative method. An attempt has been made to explore the dose response parameters of MN assay in cytokinesis-blocked lymphocytes. Whole blood was irradiated with 60 Co gamma rays or 250 kV p X rays. A dose-dependent increase in micronuclei yield was observed. The dose response could be best described by a linear-quadratic relationship for both gamma rays and X rays. The α and β coefficients were found to be 1.9 x 10 -2 Gy -1 and 5.7 x 10 -2 Gy -2 for gamma rays and 6.3 x 10 -2 Gy -1 and 4.3 x 10 -2 Gy -2 for X rays, respectively. In the low dose region X rays were three times more efficient in inducing micronuclei. The background value derived for 25 samples from healthy individuals ranged from 6-18 micronuclei per 1000 cells, with a mean value of 12 ± 4 x 10 -3 . Biological dose estimates for individuals exposed in the range 0.1-1 Gy made by MN and CA methods yielded similar results for doses ≥ 0.5 Gy. Due to the uncertainties in the background incidence of MN, at present this technique cannot provide reliable estimates at low doses. (author)

WE-B-304-03: Biological Treatment Planning

International Nuclear Information System (INIS)

Orton, C.

2015-01-01

The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations

Environmental and biological monitoring in the estimation of absorbed doses of pesticides.

Science.gov (United States)

Aprea, Maria Cristina

2012-04-25

Exposure to pesticides affects most of the population, not only persons occupationally exposed. In a context of high variability of exposure, biological monitoring is important because of the various routes by which exposure can occur and because it assesses both occupational and non-occupational exposure. The main aim of this paper was to critically compare estimates of absorbed dose measured by environmental and biological monitoring in situations in which they could both be applied. The combination of exposure measurements and biological monitoring was found to provide extremely important information on the behaviour of employees, and on the proper use and effectiveness of personal protection equipment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks.

Directory of Open Access Journals (Sweden)

Kai Rothkamm

Full Text Available Microbeam radiation therapy (MRT using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.

BEDVH--A method for evaluating biologically effective dose volume histograms: Application to eye plaque brachytherapy implants

International Nuclear Information System (INIS)

Gagne, Nolan L.; Leonard, Kara L.; Huber, Kathryn E.; Mignano, John E.; Duker, Jay S.; Laver, Nora V.; Rivard, Mark J.

2012-01-01

Purpose: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. Methods: A reference eye geometry and 16 mm COMS eye plaque loaded with 103 Pd, 125 I, or 131 Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( TUMOR D 90 ) and 10% of the organ at risk volumes ( OAR D 10 ) were calculated. The BED equation from Dale and Jones and published α/β and μ parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e., TUMOR 7 BED 10 and OAR 7 BED 10 ). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on TUMOR BEDVH and OAR BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. Results: TUMOR D 90 values were 102, 112, and 110 Gy for 103 Pd, 125 I, and 131 Cs, respectively. Corresponding TUMOR 7 BED 10 values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected, TUMOR 7 BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused TUMOR 7 BED 10 to deviate by up to 46%. Over the range of OAR α/β values, OAR 7 BED 10 varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively. Conclusions: BEDVH permits evaluation of the

Optimization of total arc degree for stereotactic radiotherapy by using integral biologically effective dose and irradiated volume

International Nuclear Information System (INIS)

Lim, Do Hoon; Kim, Dae Yong; Lee, Myung Za; Chun, Ha Chung

2001-01-01

To find the optimal values of total arc degree to protect the normal brain tissue from high dose radiation in stereotactic radiotherapy planning. With Xknife-3 planning system and 4 MV linear accelerator, the authors planned under various values of parameters. One isocenter, 12, 20, 30, 40, 50, and 60 mm of collimator diameters, 100 deg, 200 deg, 300 deg, 400 deg, 500 deg, 600 deg, of total arc degrees, and 30 deg or 45 deg of arc intervals were used. After the completion of planning, the plans were compared each other using V 50 (the volume of normal brain that is delivered high dose radiation) and integral biologically effective dose. At 30 deg of arc interval, the values of V 50 had the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval, up to 400 deg of total arc degree, the values of V 50 decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. At 30 deg of arc interval, integral biologically effective dose showed the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval with less than 40 mm collimator diameter, the integral biologically effective dose decreased with the increase of total arc degree, but with 50 and 60 mm of collimator diameters, up to 400 deg of total arc degree, integral biologically effective dose decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. In the stereotactic radiotherapy planning for brain lesions, planning with 400 deg of total arc degree is optimal. Especially, when the larger collimator more than 50 mm diameter should be used, the uses of 500 deg and 600 deg of total arc degrees make the increase of V 50 and integral biologically effective dose, Therefore stereotactic radiotherapy planning using 400 deg of total arc degree can increase the therapeutic ratio and produce the effective outcome

SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

Energy Technology Data Exchange (ETDEWEB)

Liu, G; Liu, J [Hunan University, Changsha, Hunan (China)

2016-06-15

Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vector Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer

SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

International Nuclear Information System (INIS)

Liu, G; Liu, J

2016-01-01

Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vector Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer

A Dose-Volume Analysis of Magnetic Resonance Imaging-Aided High-Dose-Rate Image-Based Interstitial Brachytherapy for Uterine Cervical Cancer

International Nuclear Information System (INIS)

Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

2010-01-01

Purpose: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Methods and Materials: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD 2 ). Results: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D 2cc of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Conclusions: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

Science.gov (United States)

Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

2010-07-01

To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results. (c) 2010 Elsevier Inc. All rights reserved.

Radiation Dose Measurement Using Chemical Dosimeters

International Nuclear Information System (INIS)

Lee, Min Sun; Kim, Eun Hee; Kim, Yu Ri; Han, Bum Soo

2010-01-01

The radiation dose can be estimated in various ways. Dose estimates can be obtained by either experiment or theoretical analysis. In experiments, radiation impact is assessed by measuring any change caused by energy deposition to the exposed matter, in terms of energy state (physical change), chemical production (chemical change) or biological abnormality (biological change). The chemical dosimetry is based on the implication that the energy deposited to the matter can be inferred from the consequential change in chemical production. The chemical dosimetry usually works on the sample that is an aqueous solution, a biological matter, or an organic substance. In this study, we estimated absorbed doses by quantitating chemical changes in matter caused by radiation exposure. Two different chemical dosimeters, Fricke and ECB (Ethanol-Chlorobenzene) dosimeter, were compared in several features including efficacy as dose indicator and effective dose range

Biological effect of Pulsed Dose Rate brachytherapy with stepping sources

International Nuclear Information System (INIS)

Limbergen, Erik F.M. van; Fowler, Jack F.

1996-01-01

Purpose: To explore the possible increase of radiation effect in tissues irradiated by pulsed brachytherapy (PDR), for local tissue dose-rates between those 'averaged over the whole pulse' and the instantaneous high dose rates close to the dwell positions. An earlier publication (Fowler and Mount 1992) had shown that, for dose rates (averaged for the duration of the pulse) up to 3 Gy/h, little change of isoeffect doses from continuous low dose rate (CLDR) are expected, unless larger doses per fraction than 1 Gy are used, and especially if components of very rapid repair are present with half-times of less than about 0.5 hours. However, local and transient dose rates close to stepping sources can be up to several Gy per minute. Methods: Calculations were done assuming the linear quadratic formula for radiation damage, in which only the dose-squared term is subject to repair, at a constant exponential rate. The formula developed by Dale for fractionated low-dose-rate radiotherapy was used. A constant overall time of 140 hours and constant total dose of 70 Gy were assumed throughout, the continuous low dose-rate of 0.5 Gy/h (CLDR) providing the unitary standard effects for each PDR condition. Effects of dose-rates ranging from 4 Gy/h to 120 Gy/h (HDR at 2 Gy/min) were studied, and T (1(2)) from 4 minutes to 1.5 hours. Results: Curves are presented relating the ratio of increased biological effect (proportional to log cell kill) calculated for PDR relative to CLDR. Ratios as high as 1.5 can be found for large doses per pulse (> 1 Gy) at high instantaneous dose-rates if T (1(2)) in tissues is as short as a few minutes. The major influences on effect are dose per pulse, half-time of repair in the tissue, and - when T (1(2)) is short - the instantaneous dose-rate. Maximum ratios of PDR/CLDR effect occur when the dose-rate is such that pulse duration is approximately equal to T (1(2)) of repair. Results are presented for late-responding tissues, the differences from CLDR

Biological dosimetry of ionizing radiation: Evaluation of the dose with cytogenetic methodologies by the construction of calibration curves

Science.gov (United States)

Zafiropoulos, Demetre; Facco, E.; Sarchiapone, Lucia

2016-09-01

In case of a radiation accident, it is well known that in the absence of physical dosimetry biological dosimetry based on cytogenetic methods is a unique tool to estimate individual absorbed dose. Moreover, even when physical dosimetry indicates an overexposure, scoring chromosome aberrations (dicentrics and rings) in human peripheral blood lymphocytes (PBLs) at metaphase is presently the most widely used method to confirm dose assessment. The analysis of dicentrics and rings in PBLs after Giemsa staining of metaphase cells is considered the most valid assay for radiation injury. This work shows that applying the fluorescence in situ hybridization (FISH) technique, using telomeric/centromeric peptide nucleic acid (PNA) probes in metaphase chromosomes for radiation dosimetry, could become a fast scoring, reliable and precise method for biological dosimetry after accidental radiation exposures. In both in vitro methods described above, lymphocyte stimulation is needed, and this limits the application in radiation emergency medicine where speed is considered to be a high priority. Using premature chromosome condensation (PCC), irradiated human PBLs (non-stimulated) were fused with mitotic CHO cells, and the yield of excess PCC fragments in Giemsa stained cells was scored. To score dicentrics and rings under PCC conditions, the necessary centromere and telomere detection of the chromosomes was obtained using FISH and specific PNA probes. Of course, a prerequisite for dose assessment in all cases is a dose-effect calibration curve. This work illustrates the various methods used; dose response calibration curves, with 95% confidence limits used to estimate dose uncertainties, have been constructed for conventional metaphase analysis and FISH. We also compare the dose-response curve constructed after scoring of dicentrics and rings using PCC combined with FISH and PNA probes. Also reported are dose response curves showing scored dicentrics and rings per cell, combining

Non-Linear Dose Response Relationships in Biology, Toxicology, and Medicine (June 8-10, 2004). Final Report

International Nuclear Information System (INIS)

Calabrese, Edward J.

2004-01-01

The conference attracts approximately 500 scientists researching in the area of non-linear low dose effects. These scientists represent a wide range of biological/medical fields and technical disciplines. Observations that biphasic dose responses are frequently reported in each of these areas but that the recognition of similar dose response relationships across disciplines is very rarely appreciated and exploited. By bringing scientist of such diverse backgrounds together who are working on the common area of non-linear dose response relationships this will enhance our understanding of the occurrence, origin, mechanism, significance and practical applications of such dose response relationships

Clinical applicability of biologically effective dose calculation for spinal cord in fractionated spine stereotactic body radiation therapy

International Nuclear Information System (INIS)

Lee, Seung Heon; Lee, Kyu Chan; Choi, Jinho; Ahn, So Hyun; Lee, Seok Ho; Sung, Ki Hoon; Kil, Se Hee

2015-01-01

The aim of the study was to investigate whether biologically effective dose (BED) based on linear-quadratic model can be used to estimate spinal cord tolerance dose in spine stereotactic body radiation therapy (SBRT) delivered in 4 or more fractions. Sixty-three metastatic spinal lesions in 47 patients were retrospectively evaluated. The most frequently prescribed dose was 36 Gy in 4 fractions. In planning, we tried to limit the maximum dose to the spinal cord or cauda equina less than 50% of prescription or 45 Gy 2/2 . BED was calculated using maximum point dose of spinal cord. Maximum spinal cord dose per fraction ranged from 2.6 to 6.0 Gy (median 4.3 Gy). Except 4 patients with 52.7, 56.4, 62.4, and 67.9 Gy 2/2 , equivalent total dose in 2-Gy fraction of the patients was not more than 50 Gy 2/2 (12.1–67.9, median 32.0). The ratio of maximum spinal cord dose to prescription dose increased up to 82.2% of prescription dose as epidural spinal cord compression grade increased. No patient developed grade 2 or higher radiation-induced spinal cord toxicity during follow-up period of 0.5 to 53.9 months. In fractionated spine SBRT, BED can be used to estimate spinal cord tolerance dose, provided that the dose per fraction to the spinal cord is moderate, e.g. < 6.0 Gy. It appears that a maximum dose of up to 45–50 Gy 2/2 to the spinal cord is tolerable in 4 or more fractionation regimen

The influence of low doses of ionizing radiation on biological systems

International Nuclear Information System (INIS)

Kwiecinska, T.

1986-11-01

Recent results concerning possible beneficial effects of low doses of ionizing radiation on biological systems are summarized. It is also pointed out on the basis of existing evidence that harmful effects on living organisms take place not only in the case of excess but also in the case of deficiency of ionizing radiation. Possibility of using radio-enhanced ultralow luminescence for studying hormesis phenomena is discussed. 24 refs., 4 figs. (author)

Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

International Nuclear Information System (INIS)

1997-11-01

The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference

KERMA-based radiation dose management system for real-time patient dose measurement

Science.gov (United States)

Kim, Kyo-Tae; Heo, Ye-Ji; Oh, Kyung-Min; Nam, Sang-Hee; Kang, Sang-Sik; Park, Ji-Koon; Song, Yong-Keun; Park, Sung-Kwang

2016-07-01

Because systems that reduce radiation exposure during diagnostic procedures must be developed, significant time and financial resources have been invested in constructing radiation dose management systems. In the present study, the characteristics of an existing ionization-based system were compared to those of a system based on the kinetic energy released per unit mass (KERMA). Furthermore, the feasibility of using the KERMA-based system for patient radiation dose management was verified. The ionization-based system corrected the effects resulting from radiation parameter perturbations in general radiography whereas the KERMA-based system did not. Because of this difference, the KERMA-based radiation dose management system might overestimate the patient's radiation dose due to changes in the radiation conditions. Therefore, if a correction factor describing the correlation between the systems is applied to resolve this issue, then a radiation dose management system can be developed that will enable real-time measurement of the patient's radiation exposure and acquisition of diagnostic images.

Biological influence from low dose and low-dose rate radiation

International Nuclear Information System (INIS)

Magae, Junji

2007-01-01

Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

International Nuclear Information System (INIS)

Iori, Mauro; Cattaneo, Giovanni Mauro; Cagni, Elisabetta; Fiorino, Claudio; Borasi, Gianni; Riccardo, Calandrino; Iotti, Cinzia; Fazio, Ferruccio; Nahum, Alan E.

2008-01-01

Background and purpose: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. Materials and methods: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. Results: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP = 5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. Conclusions: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT

Biological effects in lymphocytes irradiated with {sup 99m}Tc: determination of the curve dose-response; Efeitos biologicos em linfocitos irradiados com {sup 99m}Tc: determinacao da curva dose-resposta

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Romero Marcilio Barros Matias de

2002-08-01

Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with {sup 99m} Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with {sup 99m} Tc were used, allowing the irradiation of blood with different administered activities of {sup 99m} Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with {sup 99m} Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with {sup 99m} Tc was best fitted by the curve Y=(8,99 {+-}2,06) x 1-{sup -4} + (1,24 {+-}0,62) x 10{sup -2} D + (5,67 {+-} 0,64) x 10{sup -2} D{sup 2}. (author)

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

Science.gov (United States)

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

Energy Technology Data Exchange (ETDEWEB)

Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos [Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, TX 78229 (United States); Cheng, Chih-Yao, E-mail: shic@uthscsa.ed [Radiation Oncology Department, Oklahoma University Health Science Center, Oklahoma, OK 73104 (United States)

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V{sub 100} reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

International Nuclear Information System (INIS)

Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos; Cheng, Chih-Yao

2010-01-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V 100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

Biological dose estimation of partial body exposures in cervix cancer patients

International Nuclear Information System (INIS)

Di Giorgio, Marina; Nasazzi, Nora B.; Taja, Maria R.; Roth, B.; Sardi, M.; Menendez, P.

2000-01-01

At present, unstable chromosome aberrations analysis in peripheral blood lymphocytes is the most sensitive method to provide a biological estimation of the dose in accidental radiation over exposures. The assessment of the dose is particularly reliable in cases of acute, uniform, whole-body exposures or after irradiation of large parts of the body. However, the scenarios of most radiation accidents result in partial-body exposures or non-uniform dose distribution, leading to a differential exposure of lymphocytes in the body. Inhomogeneity produces a yield of dicentrics, which does not conform to a Poisson distribution, but is generally over dispersed. This arises because those lymphocytes in tissues outside the radiation field will not be damaged. Most of the lymphocytes (80 %) belong to the 'redistributional pool' (lymphatic tissues and other organs) and made recirculate into peripheral blood producing a mixed irradiated and unirradiated population of lymphocytes. So-called over dispersion, with a variance greater than the mean, can be taken as an indication of non-uniform exposure. The main factors operating in vivo partial-body irradiation may be the location and size of the irradiation field and, at high doses, various cellular reactions such as reduced blast transformation, mitotic delay or interphase death may contribute. For partial-body exposures, mathematical-statistical analysis of chromosome aberration data can be performed to derive a dose estimate for the irradiated fraction of the body, been more realistic than to quote a mean equivalent uniform whole body dose. The 'Contaminated Poisson' method of Dolphin or the Qdr method of Sasaki, both based on similar principles, can achieve this. Contaminated Poisson considers the over dispersed distribution of dicentrics among all the cells scored. The observed distribution is considered to be the sum of a Poisson distribution, which represents the irradiated fraction of the body, and the remaining unexposed

Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

International Nuclear Information System (INIS)

Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

2014-01-01

Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference. Refs, figs, tabs.

Implementation of spot scanning dose optimization and dose calculation for helium ions in Hyperion

Energy Technology Data Exchange (ETDEWEB)

Fuchs, Hermann, E-mail: hermann.fuchs@meduniwien.ac.at [Department of Radiation Oncology, Division of Medical Radiation Physics, Medical University of Vienna/AKH Vienna, Vienna 1090, Austria and Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna 1090 (Austria); Alber, Markus [Department for Oncology, Aarhus University Hospital, Aarhus 8000 (Denmark); Schreiner, Thomas [PEG MedAustron, Wiener Neustadt 2700 (Austria); Georg, Dietmar [Department of Radiation Oncology, Division of Medical Radiation Physics, Medical University of Vienna/AKH Vienna, Vienna 1090 (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna 1090 (Austria); Comprehensive Cancer Center, Medical University of Vienna/AKH Vienna, Vienna 1090 (Austria)

2015-09-15

Purpose: Helium ions ({sup 4}He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed and integrated into the treatment planning system Hyperion. Methods: Current knowledge on RBE of {sup 4}He together with linear energy transfer considerations motivated an empirical depth-dependent “zonal” RBE model. In the plateau region, a RBE of 1.0 was assumed, followed by an increasing RBE up to 2.8 at the Bragg-peak region, which was then kept constant over the fragmentation tail. To account for a variable proton RBE, the same model concept was also applied to protons with a maximum RBE of 1.6. Both RBE models were added to a previously developed pencil beam algorithm for physical dose calculation and included into the treatment planning system Hyperion. The implementation was validated against Monte Carlo simulations within a water phantom using γ-index evaluation. The potential benefits of {sup 4}He based treatment plans were explored in a preliminary treatment planning comparison (against protons) for four treatment sites, i.e., a prostate, a base-of-skull, a pediatric, and a head-and-neck tumor case. Separate treatment plans taking into account physical dose calculation only or using biological modeling were created for protons and {sup 4}He. Results: Comparison of Monte Carlo and Hyperion calculated doses resulted in a γ{sub mean} of 0.3, with 3.4% of the values above 1 and γ{sub 1%} of 1.5 and better. Treatment plan evaluation showed comparable planning target volume coverage for both particles, with slightly increased coverage for {sup 4}He. Organ at risk (OAR) doses were generally reduced using {sup 4}He, some by more than to 30%. Improvements of {sup 4}He over protons were more pronounced for treatment plans taking biological effects into account. All

Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

International Nuclear Information System (INIS)

Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.

2005-01-01

Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health

Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

Science.gov (United States)

Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Eric; Banzet, Nathalie; Defoort, Catherine; Bott, Romain; Dublineau, Isabelle; Aigueperse, Jocelyne; Gourmelon, Patrick; Martin, Jean-Charles; Souidi, Maâmar

2013-01-01

Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N -methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.

SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

Energy Technology Data Exchange (ETDEWEB)

Shusharina, N; Khan, F; Choi, N; Sharp, G [Massachusetts General Hospital, Boston, MA (United States)

2014-06-01

Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

International Nuclear Information System (INIS)

Shusharina, N; Khan, F; Choi, N; Sharp, G

2014-01-01

Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart

Introducing Biological Microdosimetry for Ionising Radiation

International Nuclear Information System (INIS)

Scott, B.R.; Schoellnberger, H.

2000-01-01

Microdosimetry is important for radiation protection, for understanding mechanisms of radiation action, and for radiation risk assessment. This article introduces a generic, Monte Carlo based approach to biological microdosimetry for ionising radiation. Our Monte Carlo analyses are carried out with a widely used Crystal Ball software. The approach to biological microdosimetry presented relates to quantal biological effects data (e.g. cell survival, mutagenesis, neoplastic transformation) for which there is an initial linear segment to the dose-response curve. The macroscopic dose data considered were selected such that is could be presumed that the vast majority of cells at risk have radiation dose delivered to their critical target. For cell killing, neoplastic transformation, and mutagenesis, the critical biological target for radiation is presumed to be DNA. Our approach to biological microdosimetry does not require detailed information about the mass, volume, and shape of the critical biological target. Further, one does not have to know what formal distribution function applies to the microdose distribution. However, formal distributions are required for the biological data used to derive the non-parametric microdose distributions. Here, we use the binomial distribution to characterise the variability in the number of cells affected by a fixed macroscopic dose. Assuming this variability to arise from variability in the microscopic dose to the critical biological target, a non-parametric microdose distribution is generated by the standard Monte Carlo method. The non-parametric distribution is then fitted using a set of formal distributions (beta, exponential, extreme value, gamma, logistic, log-normal, normal, Pareto, triangular, uniform, and Weibull). The best fit is then evaluated based on statistical criteria (chi-square test). To demonstrate the application of biological microdosimetry, the standard Monte Carlo method is used with radiobiological data for

Introducing Biological Microdosimetry for Ionising Radiation

Energy Technology Data Exchange (ETDEWEB)

Scott, B.R.; Schoellnberger, H

2000-07-01

Microdosimetry is important for radiation protection, for understanding mechanisms of radiation action, and for radiation risk assessment. This article introduces a generic, Monte Carlo based approach to biological microdosimetry for ionising radiation. Our Monte Carlo analyses are carried out with a widely used Crystal Ball software. The approach to biological microdosimetry presented relates to quantal biological effects data (e.g. cell survival, mutagenesis, neoplastic transformation) for which there is an initial linear segment to the dose-response curve. The macroscopic dose data considered were selected such that is could be presumed that the vast majority of cells at risk have radiation dose delivered to their critical target. For cell killing, neoplastic transformation, and mutagenesis, the critical biological target for radiation is presumed to be DNA. Our approach to biological microdosimetry does not require detailed information about the mass, volume, and shape of the critical biological target. Further, one does not have to know what formal distribution function applies to the microdose distribution. However, formal distributions are required for the biological data used to derive the non-parametric microdose distributions. Here, we use the binomial distribution to characterise the variability in the number of cells affected by a fixed macroscopic dose. Assuming this variability to arise from variability in the microscopic dose to the critical biological target, a non-parametric microdose distribution is generated by the standard Monte Carlo method. The non-parametric distribution is then fitted using a set of formal distributions (beta, exponential, extreme value, gamma, logistic, log-normal, normal, Pareto, triangular, uniform, and Weibull). The best fit is then evaluated based on statistical criteria (chi-square test). To demonstrate the application of biological microdosimetry, the standard Monte Carlo method is used with radiobiological data for

The radioinduced membranes injuries as biological dose indicators: mechanisms of studies and practical applications

International Nuclear Information System (INIS)

Vincent-Genod, Lucie

2001-10-01

After an accidental overexposure, the assessment of the received dose in biological dosimetry is performed by a method based on the effects of irradiation on the DNA molecule. But this technique shows some limitations; therefore we tried to find new bio-sensors of radiation exposure. We have pointed out that membrane is a critical target of ionising radiation after an in vitro and in vivo overexposure. In vitro, these modifications were involved in the radio-induced apoptotic pathway. The measure of membrane fluidity allowed us to obtain an overall view of cellular membrane. Moreover, in vivo, by changing the lipid nutritional status of animals, our results displayed the important role played by membrane lipid composition in radio-induced membrane alterations. Besides, membrane effects were adjusted by the extracellular physiological control, and in particular by the damages on membrane fatty acid pattern. Finally, we have tested the use of membrane fluidity index as a bio-sensor of radiation exposure on in vivo models and blood samples from medical total body irradiated patients. The results achieved on animal models suggested that the membrane fluidity index was a bio-sensor of radiation exposure. Nevertheless, the observations realised on patients highlight that the effect of the first dose fraction of the radiotherapy treatment had some difficulties to be noticed. Indeed, the combined treatment: chemotherapy and radiotherapy disturbed the membrane fluidity index measures. To conclude, whereas this parameter was not a bio-sensor of irradiation exposure usable in biological dosimetry, it may allow us to assess the radio-induced damages and their cellular but also tissue impacts. (author)

A perspective on dose limits and biological effects of radiation on the foetus

International Nuclear Information System (INIS)

Myers, D.K.; Gordon, K.

1992-01-01

The potential biological effects of radiation doses to pregnant workers consistent with Canadian regulations and ICRP recommendations are reviewed. These hazards are in general very small compared to the normal hazards associated with human development. Potential carcinogenic effects may well be the major biological problem associated with foetal exposures. Radiation hazards to the embryo are essentially zero for exposures occurring during the first four weeks after conception. The new ICRP recommendations on exposures of pregnant women suggest a number of problems to be solved. These include (a) improvements in current methods of measuring both external radiation doses and intakes of certain radionuclides in Canada, (b) further research on the metabolism of radionuclides in pregnant women, including concentrations of certain radionuclides in foetal/embryonic tissues and also in adjacent tissues of the mother; and (c) socio-economic problems that may be involved in the implementation of the recommendations on exposures of pregnant workers, particularly in small facilities such as nuclear medicine departments in hospitals. (Author) 3 tabs., 21 refs

Influence of variations in dose and dose rates on biological effects of inhaled beta-emitting radionuclides

International Nuclear Information System (INIS)

McClellan, R.O.; Benjamin, S.A.; Boecker, B.B.; Hahn, F.F.; Hobbs, C.H.; Jones, R.K.; Lundgren, D.L.

1976-01-01

The biological effects of inhaled β-emitting radionuclides, 90 Y, 91 Y, 144 Ce and 90 Sr, are being investigated in beagle dogs that received single acute exposures at 12 to 14 months of age. The aerosols studied have included 91 YC1 3 , 144 CeC1 3 , 90 SrC1 2 , and 90 Y, 91 Y, 144 Ce or 90 Sr in aluminosilicate particles. Thus, 91 YCl 3 , 144 CeCl 3 and the aluminosilicate containing radionuclide particles all resulted in significant exposures to lung; 91 YC1 3 , 144 CeC1 3 an 90 SrC1 2 resulted in significant exposures to bone; 91 YC1 3 and 144 CeC1 3 resulted in significant exposures to liver. The higher initial doserate exposures have been more effective than low dose-rate exposures on a per-rad basis in producing early effects. To date ( 144 CeO 2 , it was observed that, on a μCi initial lung burden per kilogram body weight basis, mice did not develop pulmonary tumours whereas beagle dogs did. To fid out the reason for this observation mice have been repeatedly exposed by inhalation to 144 CeO 2 to maintain lung burdens of 144 Ce that resulted in radiation dose rates similar to that observed in beagle dogs. Several of the repeatedly exposed mice developed malignant pulmonary tumours. Thus, with similar dose rates and cumulative doses to the lung, mice and dogs responded in a similar manner to chronic β radiation

Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

International Nuclear Information System (INIS)

Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

2007-01-01

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans

International Nuclear Information System (INIS)

Liang, X.; Penagaricano, J.; Zheng, D.; Morrill, S.; Zhang, X.; Corry, P.; Griffin, R. J.; Han, E. Y.; Hardee, M.; Ratanatharathom, V.

2016-01-01

The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D 95% ) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower

Feasibility of TCP-based dose painting by numbers applied to a prostate case with 18F-choline PET imaging

International Nuclear Information System (INIS)

Dirscherl, Thomas; Bogner, Ludwig; Rickhey, Mark

2012-01-01

Introduction: A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Method and Materials: Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with 18 F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. Results: When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100 Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1 Gy to 99.3 Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64 Gy and a standard deviation of 4.02 Gy. Film verification showed a reasonable agreement of planned and delivered dose. Conclusion: If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. (orig.)

Radiation-induced temporary partial epilation in the pig: a biological indicator of radiation dose and dose distribution to the skin

International Nuclear Information System (INIS)

Sieber, V.K.; Hopewell, J.W.

1990-01-01

Radiation damage to the matrix cells of actively growing hairs can result in transient epilation in the pig, the severity of which can be assessed using a visual scoring system. The extent of hair loss was found to be dose-dependent for single doses in the range 6 - 14 Gy for 250 kV X rays. The ED 50 for detectable hair loss was 9.83 ± 0.58 Gy whilst that for the loss of > 50% of hairs was 13.78 ± 0.90 Gy. The system is simple, non-invasive and would appear to have considerable potential for use in biological dosimetry for high exposures that are likely to require local treatment. (author)

The biological response of plucked human hair to low-dose radiation: a measure of individual radiosensitivity and a technique for biological dosimetry

International Nuclear Information System (INIS)

Swain, D.

1997-01-01

It is often assumed that the effects of radiation are linear with dose and that high dose effects can be extrapolated to low dose levels. However, there are a variety of mechanisms which can alter the response at low doses. The most important of these relate to induced sensitivity or induced repair mechanisms. It is therefore important that this area is studied in more depth by looking at the molecular effects and damage to cells at low doses. It is well known that there are certain rare genetic syndromes which predispose individuals to cancer, e.g. ataxia telangiectasia. It is also probable that there is a large range of sensitivity in the natural variation of individuals to the risk of radiation-induced cancer. It is proposed that radiosensitivity is studied using stimulated lymphocytes from whole blood and the technique extended to look at the effects in cell cultures established from human hair. Radiation treatment of cell cultures established from plucked human hair has been previously advocated as a non-invasive technique for non-uniform biological dosimetry and it is proposed that these techniques are adapted to the use of hair to estimate individual radiosensitivity. The aim is to establish and optimize these techniques for culturing keratinocytes from plucked human hair follicles with a view to study biological markers for the subsequent assessment of radiosensitivity. Preliminary results are promising and suggest that the technique for culturing keratinocytes from hair presents a feasible approach. Results from this primary cell culture technique and results from the comparison of the micronuclei data obtained from the cell cultures and stimulated lymphocytes will be presented. (author)

Impact of respiratory motion on variable relative biological effectiveness in 4D-dose distributions of proton therapy.

Science.gov (United States)

Ulrich, Silke; Wieser, Hans-Peter; Cao, Wenhua; Mohan, Radhe; Bangert, Mark

2017-11-01

Organ motion during radiation therapy with scanned protons leads to deviations between the planned and the delivered physical dose. Using a constant relative biological effectiveness (RBE) of 1.1 linearly maps these deviations into RBE-weighted dose. However, a constant value cannot account for potential nonlinear variations in RBE suggested by variable RBE models. Here, we study the impact of motion on recalculations of RBE-weighted dose distributions using a phenomenological variable RBE model. 4D-dose calculation including variable RBE was implemented in the open source treatment planning toolkit matRad. Four scenarios were compared for one field and two field proton treatments for a liver cancer patient assuming (α∕β) x  = 2 Gy and (α∕β) x  = 10 Gy: (A) the optimized static dose distribution with constant RBE, (B) a static recalculation with variable RBE, (C) a 4D-dose recalculation with constant RBE and (D) a 4D-dose recalculation with variable RBE. For (B) and (D), the variable RBE was calculated by the model proposed by McNamara. For (C), the physical dose was accumulated with direct dose mapping; for (D), dose-weighted radio-sensitivity parameters of the linear quadratic model were accumulated to model synergistic irradiation effects on RBE. Dose recalculation with variable RBE led to an elevated biological dose at the end of the proton field, while 4D-dose recalculation exhibited random deviations everywhere in the radiation field depending on the interplay of beam delivery and organ motion. For a single beam treatment assuming (α∕β) x  = 2 Gy, D 95 % was 1.98 Gy (RBE) (A), 2.15 Gy (RBE) (B), 1.81 Gy (RBE) (C) and 1.98 Gy (RBE) (D). The homogeneity index was 1.04 (A), 1.08 (B), 1.23 (C) and 1.25 (D). For the studied liver case, intrafractional motion did not reduce the modulation of the RBE-weighted dose postulated by variable RBE models for proton treatments.

Exposures at low doses and biological effects of ionizing radiations

International Nuclear Information System (INIS)

Masse, R.

2000-01-01

Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

International Nuclear Information System (INIS)

Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

2010-01-01

Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS.

Science.gov (United States)

Ainsbury, Elizabeth A; Samaga, Daniel; Della Monaca, Sara; Marrale, Maurizio; Bassinet, Celine; Burbidge, Christopher I; Correcher, Virgilio; Discher, Michael; Eakins, Jon; Fattibene, Paola; Güçlü, Inci; Higueras, Manuel; Lund, Eva; Maltar-Strmecki, Nadica; McKeever, Stephen; Rääf, Christopher L; Sholom, Sergey; Veronese, Ivan; Wieser, Albrecht; Woda, Clemens; Trompier, Francois

2018-03-01

Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the 'EURADOS Working Group 10-Retrospective dosimetry' members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.

Comparison in the determination of absorbed dose by biological and physical methods to patients in treatment of cardiac intervention

International Nuclear Information System (INIS)

Guerrero C, C.; Arceo M, C.

2014-10-01

The use of less invasive procedures, lower risk and quick recovery as cardiac intervention have proven to be an efficient alternative to reestablish the correct bloodstream of the patient. In this case the patient is subjected to values of absorbed dose above to which is subjected in a study with X-rays for medical diagnosis, and this can cause radiation injuries to the skin. The target organ, in this case can be exposed to doses of 2 Gy above. Different methods to estimate the dose were use, physical by Radiochromic film, as biological by dicentric analysis. Both methods provided additional information demonstrating thus the risk in the target organ and the patient. The most reliable biological indicator of exposure to ionizing radiation is the study of chromosomal aberrations, specifically dicentric in human lymphocytes. This test allowed establishing the exposure dose depending of the damage. (Author)

Modification of the biologic dose to normal tissue by daily fraction

Energy Technology Data Exchange (ETDEWEB)

Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

1976-12-01

A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

Biologically-equivalent dose and long-term survival time in radiation treatments

International Nuclear Information System (INIS)

Zaider, Marco; Hanin, Leonid

2007-01-01

Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

Biological effects of low-dose radiation on human population living in high-background radiation areas of Kerala coast

International Nuclear Information System (INIS)

Das, Birajalaxmi

2016-01-01

High-level natural radiation areas (HLNRA) of Kerala coast is densely populated and known for its wide variation in background radiation dose levels due to uneven distribution of monazite in the beach sand. The background radiation dose varies from 1 to 45 mGv/y. The areas with >1.5mGy/y is considered as HLNRA. Human population inhabiting in this area are exposed to low-dose chronic radiation since generations. Hence, this population provides an ideal situation to study dose response and adaptive response, if any, due to natural chronic low-dose exposure. It has been investigated extensively to study the biological and health effects of long-term low-dose/low-dose radiation exposure. So far over 150, 000 newborns monitored from hospital-based study did not reveal any significant difference in the incidence of any of the malformations and stillbirth between HLNRA and adjacent control areas. A case-control study on cleft lip/palate and mental retardation did not show any association with background radiation dose. Cytogenetic investigation of over 27,000 newborns did not show any significant increase in the frequency of chromosome aberrations and karyotype anomalies. DNA damage endpoints, such as micronuclei, telomere length and DNA strand breaks, did not reveal any significant difference between control and exposed population. Studies on DNA damage and repair revealed efficient repair of DNA strand breaks in HLNRA individuals. Molecular studies using high throughput microarray analysis indicated a large number of genes involved in various molecular and cellular pathways. Indications of in vivo radioadaptive response due to natural chronic low-dose exposure in this population have important implications to human health. (author)

Radiosensitivity of Nicotiana protoplasts. Action on cell; cycle effects of low dose and fractionated irradiations; biological repair

International Nuclear Information System (INIS)

Magnien, E.

1981-10-01

Leaf protoplasts of Nicotiana plumbaginifolia and Nicotiana sylvestris demonstrate five main qualities: they can be maintained as haploid lines; they constitute starting populations with a remarkable cytological homogeneity; they show a transient initial lag-phase; they yield very high plating efficiencies and retain permanently a complete differentiation capacity; being derived of a cell wall, they appear well adapted for fusion experiments or enzymatic dosages. The resumption of mitotic activity was followed by cytophotometric measurements, labelling experiments, nuclear sizing and enzymatic assays. The action of 5 Gy gamma-ray irradiations delayed entrance in the S-phase, provoked an otherwise not verified dependency between transcription, translation and protein synthesis, increased nuclear volumes in the G2-phase, and slightly stimulated the activity of a repair enzyme. The plating efficiency was a sensitive end-point which allowed the evaluation of the biological effectiveness of low to medium radiation-doses after gamma-ray and fast neutron irradiations. The neutron dose-RBE relationship increased from 3 to 25 when the dose decreased from 5 Gy to 5 mGy. When fractionated into low single doses only, a neutron dose of 300 mGy markedly increased its biological effectiveness: this phenomenon could not be explained by cell progression, and necessitated additional hypotheses involving other mechanisms in the specific action of low radiation doses. Radiation-induced UDS was measured in presence of aphidicolin. A beta-like DNA-polymerase was shown to be definitely involved in nuclear repair synthesis [fr

A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

Directory of Open Access Journals (Sweden)

Raffaella Marconi

Full Text Available Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR. In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects.We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED. To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells.Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated.Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice.

Activation of chemical biological defense mechanisms and remission of vital oxidative injury by low dose radiation

International Nuclear Information System (INIS)

Yamaoka, K.; Nomura, T.; Kojima, S.

2000-01-01

Excessive active oxygen produced in vivo by various causes is toxic. Accumulation of oxidation injuries due to excessive active causes cell and tissue injuries, inducing various pathologic conditions such as aging and carcinogenesis. On the other hand, there are chemical defense mechanisms in the body that eliminate active oxygen or repair damaged molecules, defending against resultant injury. It is interesting reports that appropriate oxidation stress activate the chemical biological defense mechanisms. In this study, to elucidate these phenomena and its mechanism by low dose radiation, we studied on the below subjects. Activation of chemical biological defense mechanisms by low dose radiation: (1) The effects radiation on lipid peroxide (LPO) levels in the organs, membrane fluidity and the superoxide dismutase (SOD) activity were examined in rats and rabbits. Rats were irradiated with low dose X-ray over their entire bodies, and rabbits inhaled vaporized radon spring water, which primarily emitted α-ray. The following results were obtained. Unlike high dose X-ray, low dose X-ray and radon inhalation both reduced LPO levels and made the state of the SH-group on membrane-bound proteins closer to that of juvenile animals, although the sensitivity to radioactivity varied depending on the age of the animals and among different organs and tissues. The SOD activity was elevated, suggesting that low dose X-ray and radon both activate the host defensive function. Those changes were particularly marked in the organs related to immune functions of the animals which received low dose X-ray, while they were particularly marked in the brain after radon inhalation. It was also found that those changes continued for longer periods after low dose X-irradiation. (2) Since SOD is an enzyme that mediates the dismutation of O 2 - to H 2 O 2 , the question as to whether the resultant H 2 O 2 is further detoxicated into H 2 O and O 2 or not must still be evaluated. Hence, we studied

Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

Science.gov (United States)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Optimum dose of 2-hydroxyethyl methacrylate based bonding material on pulp cells toxicity

OpenAIRE

Saraswati, Widya

2010-01-01

Background: 2-hydroxyethyl methacrylate (HEMA), one type of resins commonly used as bonding base material, is commonly used due to its advantageous chemical characteristics. Several preliminary studies indicated that resin is a material capable to induce damage in dentin-pulp complex. It is necessary to perform further investigation related with its biological safety for hard and soft tissues in oral cavity. Purpose: The author performed an in vitro test to find optimum dose of HEMA resin mon...

The biological basis for dose limitation to the skin

International Nuclear Information System (INIS)

Fry, R.J.M.

1992-01-01

Ionizing radiation may cause deterministic effects and cancer. It has been the policy to base dose limits for radiation protection of the skin on the prevention of deterministic effects (1). In the case of cancer in general, dose limitation for radiation protection is based on limiting excess cancer mortality to low levels of radiation. Since skin cancers are seldom lethal, the general radiation protection standards will protect against an increase in excess mortality from skin cancer. However, with the dose limits selected to prevent deterministic effects, there is a significant probability of an excess incidence of skin cancer occurring as a result of exposure during a working lifetime. The induction of skin cancer by radiation is influenced significantly by subsequent exposure to ultraviolet radiation (UVR) from sunlight. This finding raises not only interesting questions about the mechanisms involved, but also about the differences in risk of skin cancer in different populations. The amount and distribution of melanin in the skin determines the degree of the effect of UVR. This paper discusses the mechanisms of the induction of both deterministic and stochastic effects in skin exposed to radiation in relation to radiation protection. (author)

Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

International Nuclear Information System (INIS)

Soehn, Matthias; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

2007-01-01

Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse

Relative biological effectiveness of alpha-particle emitters in vivo at low doses

International Nuclear Information System (INIS)

Howell, R.W.; Azure, M.T.; Narra, V.R.; Rao, D.V.

1994-01-01

The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 - 6.1 x 10 -2 LET + 1.0 x 10 -3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by RBE α = 22 E α -0.73 . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters. 46 refs., 6 figs

Biology task group

International Nuclear Information System (INIS)

Anon.

1981-01-01

The accomplishments of the task group studies over the past year are reviewed. The purposes of biological investigations, in the context of subseabed disposal, are: an evaluation of the dose to man; an estimation of effects on the ecosystem; and an estimation of the influence of organisms on and as barriers to radionuclide migration. To accomplish these ends, the task group adopted the following research goals: (1) acquire more data on biological accumulation of specific radionuclides, such as those of Tc, Np, Ra, and Sr; (2) acquire more data on transfer coefficients from sediment to organism; (3) Calculate mass transfer rates, construct simple models using them, and estimate collective dose commitment; (4) Identify specific pathways or transfer routes, determine the rates of transfer, and make dose limit calculations with simple models; (5) Calculate dose rates to and estimate irradiation effects on the biota as a result of waste emplacement, by reference to background irradiation calculations. (6) Examine the effect of the biota on altering sediment/water radionuclide exchange; (7) Consider the biological data required to address different accident scenarios; (8) Continue to provide the basic biological information for all of the above, and ensure that the system analysis model is based on the most realistic and up-to-date concepts of marine biologists; and (9) Ensure by way of free exchange of information that the data used in any model are the best currently available

IMRT optimization with pseudo-biologic objective function

International Nuclear Information System (INIS)

Yi, B. Y.; Ahn, S. D.; Kim, J. H.; Lee, S. W.; Choi, E. K.

2002-01-01

The pseudo-biologic objective function has been proposed for the IMRT optimization. It is similar to the biological objective function in mathematical shape, but uses physical parameters. The pseudo-biologic objective function concept is consisted of the target coverage index (TCI) and the organ score index (OSI), was introduced. The TCI was expressed as the sum of all of the weighted bins of target dose volume histogram (DVH). The weights were given as the normal distribution of which the average is 100 % and the standard deviation is ±. The OSI was expressed as similar way. The average of the normal distribution was 0% of the dose and that of standard deviation was selected as a function of limiting dose and its importance. The objective function could be calculated as the product of the TCI and OSI's. The RTP Tool Box (RTB) was used for this study. The constraints applied in the optimization was intuitively clinical experience based numbers, while the physical objective function asks just numbers which are not necessarily based on the clinic, and the parameters for the biologic objective functions are uncertain. The OSI's from the pseudo-biological function showed better results than from the physical functions, while TCI's showed similar tendency. We could show that the pseudo-biologic function can be used for an IMRT objective function on behalf of the biological objective function

Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

Science.gov (United States)

Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

2011-12-01

Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

Generation of Composite Dose and Biological Effective Dose (BED) Over Multiple Treatment Modalities and Multistage Planning Using Deformable Image Registration

International Nuclear Information System (INIS)

Zhang, Geoffrey; Huang, T-C; Feygelman, Vladimir; Stevens, Craig; Forster, Kenneth

2010-01-01

Currently there are no commercially available tools to generate composite plans across different treatment modalities and/or different planning image sets. Without a composite plan, it may be difficult to perform a meaningful dosimetric evaluation of the overall treatment course. In this paper, we introduce a method to generate composite biological effective dose (BED) plans over multiple radiotherapy treatment modalities and/or multistage plans, using deformable image registration. Two cases were used to demonstrate the method. Case I was prostate cancer treated with intensity-modulated radiation therapy (IMRT) and a permanent seed implant. Case II involved lung cancer treated with two treatment plans generated on two separate computed tomography image sets. Thin-plate spline or optical flow methods were used as appropriate to generate deformation matrices. The deformation matrices were then applied to the dose matrices and the resulting physical doses were converted to BED and added to yield the composite plan. Cell proliferation and sublethal repair were considered in the BED calculations. The difference in BED between normal tissues and tumor volumes was accounted for by using different BED models, α/β values, and cell potential doubling times. The method to generate composite BED plans presented in this paper provides information not available with the traditional simple dose summation or physical dose summation. With the understanding of limitations and uncertainties of the algorithms involved, it may be valuable for the overall treatment plan evaluation.

Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives

International Nuclear Information System (INIS)

Chen Zhe; Nath, Ravinder

2003-01-01

Purpose: To develop a tool for evaluating interstitial seed implants that contain a mixture of radionuclides with different half-lives and to demonstrate its utility by examining the clinical implications of prescribing to an isodose surface for such an implant. Methods and Materials: A linear-quadratic model for continuous low dose rate irradiation was developed for permanent implants containing a mixture of radionuclides. Using a generalized equation for the biologically effective dose (BED), the effects of cell proliferation and sublethal damage repair were examined systematically for implants containing a mixture of radionuclides. A head-and-neck permanent seed implant that contained a mixture of 125 I and 103 Pd seeds was used to demonstrate the utility of the generalized BED. Results: An equation of BED for implants containing a mixture of radionuclides with different half-lives was obtained. In such an implant, the effective cell kill was shown to depend strongly on the relative dose contributions from each radionuclide type; dose delivered by radionuclides with shorter half-life always resulted in more cell kill for any given sublethal damage repair and cell proliferation rates. Application of the BED formula to an implant containing a mixture of 125 I and 103 Pd seeds demonstrates that the conventional dose prescription to an isodose surface is not unique for such an implant. When the prescription dose was based on existing clinical experience of using 125 I seeds alone, mixing 103 Pd seeds with 125 I seeds would increase the cell kill. On the other hand, if the prescription dose were based on existing clinical experience of using 103 Pd seeds alone, mixing 125 I seeds with 103 Pd seeds in the same implant would create radiobiologically 'cold' spots (i.e., an increase in cell survival) at locations where a major portion of the prescription dose is contributed by the 125 I seeds. For fast-growing tumors, these 'cold' spots can become significant

Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

Science.gov (United States)

Lumen, Annie; Mattie, David R; Fisher, Jeffrey W

2013-06-01

A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

Science.gov (United States)

O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

2017-09-01

The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

Biological dosimetry - a Bayesian approach in the presentation of the uncertainty of the estimated dose in cases of exposure to low dose radiation

International Nuclear Information System (INIS)

Di Giorgio, Marina; Zaretzky, A.

2010-01-01

Biodosimetry laboratory experience has shown that there are limitations in the existing statistical methodology. Statistical difficulties generally occur due to the low number of aberrations leading to large uncertainties for dose estimation. Some problems derived from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something fixed and consequently provides a deterministic dose estimation and associated confidence limits. On the other hand, recipients of biological dosimetry reports, including medical doctors, regulators and the patients themselves may have a limited comprehension of statistics and of informed reports. Thus, the objective of the present paper is to use a Bayesian approach to present the uncertainty on the estimated dose to which a person could be exposed, in the case of low dose (occupational doses) radiation exposure. Such methodology will allow the biodosimetrists to adopt a probabilistic approach for the cytogenetic data analysis. At present, classical statistics allows to produce a confidence interval to report such dose, with a lower limit that could not detach from zero. In this situation it becomes difficult to make decisions as they could impact on the labor activities of the worker if an exposure exceeding the occupational dose limits is inferred. The proposed Bayesian approach is applied to occupational exposure scenario to contribute to take the appropriate radiation protection measures. (authors) [es

Radiation dose and biological effects to mouse testis from sodium 32P-phosphate

International Nuclear Information System (INIS)

Mian, T.A.; Glenn, H.J.; Haynie, T.P.; Meistrich, M.L.

1982-01-01

Radiation dose to mouse testis was estimated to be about 1.65 rad per μCi of intravenously injected 32 P. This high dose to the organ was due to the incorporation of this isotope into the macromolecules of the testis. Up to 30% of the total testis activity was in DNA molecules. Biologic effects on mouse testis from 32 P were determined by testis weight loss and the decrease in the number of sperm heads in the testis. Number of sperm heads reached a minimum of 1.3% of control 36 days after injection of 3.5 μCi/g body weight of 32 P. Significant decreases in sperm head counts were observed after as little as 0.2 μCi/g body weight of 32 P. (author)

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

Directory of Open Access Journals (Sweden)

Devaraj Jayachandran

Full Text Available 6-Mercaptopurine (6-MP is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN through enzymatic reaction involving thiopurine methyltransferase (TPMT. Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

Science.gov (United States)

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Embracing model-based designs for dose-finding trials.

Science.gov (United States)

Love, Sharon B; Brown, Sarah; Weir, Christopher J; Harbron, Chris; Yap, Christina; Gaschler-Markefski, Birgit; Matcham, James; Caffrey, Louise; McKevitt, Christopher; Clive, Sally; Craddock, Charlie; Spicer, James; Cornelius, Victoria

2017-07-25

Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators' preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.

Radiation biology. Chapter 20

Energy Technology Data Exchange (ETDEWEB)

Wondergem, J. [International Atomic Energy Agency, Vienna (Austria)

2014-09-15

Radiation biology (radiobiology) is the study of the action of ionizing radiations on living matter. This chapter gives an overview of the biological effects of ionizing radiation and discusses the physical, chemical and biological variables that affect dose response at the cellular, tissue and whole body levels at doses and dose rates relevant to diagnostic radiology.

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

Science.gov (United States)

Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

2017-01-01

We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

Image noise-based dose adaptation in dynamic volume CT of the heart: dose and image quality optimisation in comparison with BMI-based dose adaptation

Energy Technology Data Exchange (ETDEWEB)

Odedra, Devang [Queen' s University, School of Medicine, Kingston, ON (Canada); Blobel, Joerg [Toshiba Medical Systems Europe BV, Zoetermeer (Netherlands); University of Toronto, Division of Cardiothoracic Imaging, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); AlHumayyd, Saad; Durand, Miranda; Jimenez-Juan, Laura; Paul, Narinder [University of Toronto, Division of Cardiothoracic Imaging, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

2014-01-15

To compare the image quality and radiation dose using image-noise (IN)-based determination of X-ray tube settings compared with a body mass index (BMI)-based protocol during CT coronary angiography (CTCA). Two hundred consecutive patients referred for CTCA to our institution were divided into two groups: BMI-based, 100 patients had CTCA with the X-ray tube current adjusted to the patient's BMI while maintaining a fixed tube potential of 120 kV; IN-based, 100 patients underwent imaging with the X-ray tube current and voltage adjusted to the IN measured within the mid-left ventricle on a pre-acquisition trans-axial image. Two independent cardiac radiologists performed blinded image quality assessment with quantification of the IN and signal-to-noise ratio (SNR) from the mid-LV and qualitative assessment using a three-point score. Radiation dose (CTDI and DLP) was recorded from the console. Results showed: IN (HU): BMI-based, 30.1 ± 9.9; IN-based, 33.1 ± 6.7; 32 % variation reduction (P = 0.001); SNR: BMI-based, 18.6 ± 7.1; IN-based, 15.4 ± 3.7; 48 % variation reduction (P < 0.0001). Visual scores: BMI-based, 2.3 ± 0.6; IN-based, 2.2 ± 0.5 (P = 0.54). Radiation dose: CTDI (mGy), BMI-based, 22.68 ± 8.9; IN-based, 17.16 ± 7.6; 24.3 % reduction (P < 0.001); DLP (mGy.cm), BMI-based, 309.3 ± 127.5; IN-based, 230.6 ± 105.5; 25.4 % reduction (P < 0.001). Image-noise-based stratification of X-ray tube parameters for CTCA results in 32 % improvement in image quality and 25 % reduction in radiation dose compared with a BMI-based protocol. (orig.)

Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

Science.gov (United States)

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

2010-02-01

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell

CT dose reduction in children

International Nuclear Information System (INIS)

Vock, Peter

2005-01-01

World wide, the number of CT studies in children and the radiation exposure by CT increases. The same energy dose has a greater biological impact in children than in adults, and scan parameters have to be adapted to the smaller diameter of the juvenile body. Based on seven rules, a practical approach to paediatric CT is shown: Justification and patient preparation are important steps before scanning, and they differ from the preparation of adult patients. The subsequent choice of scan parameters aims at obtaining the minimal signal-to-noise ratio and volume coverage needed in a specific medical situation; exposure can be divided in two aspects: the CT dose index determining energy deposition per rotation and the dose-length product (DLP) determining the volume dose. DLP closely parallels the effective dose, the best parameter of the biological impact. Modern scanners offer dose modulation to locally minimise exposure while maintaining image quality. Beyond the selection of the physical parameters, the dose can be kept low by scanning the minimal length of the body and by avoiding any non-qualified repeated scanning of parts of the body. Following these rules, paediatric CT examinations of good quality can be obtained at a reasonable cost of radiation exposure. (orig.)

Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [3H] hydrocortisone

International Nuclear Information System (INIS)

Voigt, J.; Grote, H.; Sekeris, C.E.

1981-01-01

After administration of [ 3 H] hydrocortisone to adrenalectomized rats, hormone-protein complexes were isolated from liver cytosol by DEAE-cellulose chromatography. After application of biologically active and inactive doses of hydrocortisone five binding components were detected eluting at the same salt concentrations as the hormone-protein complexes observed after incubation of cytosol with [ 3 H] hydrocortisone in vitro. The isolated hormone-protein fractions were acidified and extracted with ethylacetate and the steroids were analyzed by thin-layer chromatography. No significant amount of hydrocortisone could be detected in any of the complexes formed in vivo 5-60 min after administration of biologically active doses of hydrocortisone. 3xi,11β,17α,20xi, 21-Pentahydroxypregnane, steroidal carboxy acids, glucuronides and a very polar conjugate of hydrocortisone were found in the different fractions. After an in vivo dose of hydrocortisone of about 1/5000th of the minimal dose required for enzyme induction, hydrocortisone could be found in all the cytoplasmic hormone-protein complexes formed. In contrast to the cytoplasmic hormone-protein complexes, hydrocortisone could be readily demonstrated in nuclei isolated after the administration of biologically active doses of hormone, although acid metabolites were found to represent the main part of the radioactive compounds present in the nuclei. These acid metabolites were located in the nuclear envelope. (orig.)

Validation of GPU based TomoTherapy dose calculation engine.

Science.gov (United States)

Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

2012-04-01

The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Qin, N; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States); Peeler, C [UT MD Anderson Cancer Center, Houston, TX (United States); Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

Can results from animal studies be used to estimate dose or low dose effects in humans

International Nuclear Information System (INIS)

Thomas, J.M.; Eberhardt, L.L.

1981-01-01

A method has been devised to extrapolate biological equilibrium levels between animal species and subsequently to humans. Our initial premise was based on the observation that radionuclide retention is normally a function of metabolism so that direct or indirect measures could be described by a power law based on body weights of test animal species. However, we found that such interspecies comparisons ought to be based on the coefficient of the power equation rather than on the exponential parameter. The method is illustrated using retention data obtained from five non-ruminant species (including humans) that were fed radionuclides with different properties. It appears that biological equilibrium level for radionuclides in man can be estimated using data from mice, rats, and dogs. The need to extrapolate low-dose effects data obtained from small animals (usually rodents) to humans is not unique to radiation dosimetry or radiation protection problems. Therefore, some quantitative problems connected with estimating low-dose effects from other disciplines have been reviewed, both because of the concern about effects induced by the radionuclide moiety of a radiopharmaceutical and those of the nonradioactive component. The possibility of extrapolating low-dose effects calculated from animal studies to human is discussed

Can results from animal studies be used to estimate dose or low dose effects in humans

International Nuclear Information System (INIS)

Thomas, J.M.; Eberhardt, L.L.

1981-01-01

We have devised a method to extrapolate biological equilibrium levels between animal species and subsequently to humans. Our initial premise was based on the observation that radionuclide retention is normally a function of metabolism so that direct or indirect measures could be described by a power law based on body weights of test animal species. However, we found that such interspecies comparisons ought to be based on the coefficient of the power equation rather than on the exponential parameter. The method is illustrated using retention data obtained from five non-ruminant species (including humans) that were fed radionuclides with different properties. It appears that biological equilibrium level for radionuclides in man can be estimated using data from mice, rats and dogs. The need to extrapolate low-dose effects data obtained from small animals (usually rodents) to humans is not unique to radiation dosimetry or radiation protection problems. Therefore, researchers have reviewed some quantitative problems connected with estimating low-dose effects from other disciplines, both because of the concern about effects induced by the radionuclide moiety of a radiopharmaceutical and those of the nonradioactive component. The possibility of extrapolating low-dose effects calculated from animal studies to humans is discussed

The biological effects of high dose total body irradiation in beagle dogs

International Nuclear Information System (INIS)

Luo Qingliang; Liu Xiaolan; Hao Jing; Xiong Guolin; Dong Bo; Zhao Zhenhu; Xia Zhengbiao; Qiu Liling; Mao Bingzhi

2002-01-01

Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by 60 Co sources at 7.224 x 10 -2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

Confectionery-based dose forms.

Science.gov (United States)

Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

2015-01-01

Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

Model of organ dose combination

International Nuclear Information System (INIS)

Valley, J.-F.; Lerch, P.

1977-01-01

The ICRP recommendations are based on the limitation of the dose to each organ. In the application and for a unique source the critical organ concept allows to limit the calculation and represents the irradiation status of an individuum. When several sources of radiation are involved the derivation of the dose contribution of each source to each organ is necessary. In order to represent the irradiation status a new parameter is to be defined. Propositions have been made by some authors, in particular by Jacobi introducing at this level biological parameters like the incidence rate of detriment and its severity. The new concept is certainly richer than a simple dose notion. However, in the actual situation of knowledge about radiation effects an intermediate parameter, using only physical concepts and the maximum permissible doses to the organs, seems more appropriate. The model, which is a generalization of the critical organ concept and shall be extended in the future to take the biological effects into account, will be presented [fr

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

International Nuclear Information System (INIS)

Orton, C; Borras, C; Carlson, D

2014-01-01

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

Energy Technology Data Exchange (ETDEWEB)

Orton, C [Wayne State University, Grosse Pointe, MI (United States); Borras, C [Radiological Physics and Health Services, Washington, DC (United States); Carlson, D [Yale University School of Medicine, New Haven, CT (United States)

2014-06-15

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

Statistical issues in biological radiation dosimetry for risk assessment using stable chromosome aberrations

International Nuclear Information System (INIS)

Cologne, J.B.; Preston, D.L.

1998-01-01

Biological dosimeters are useful for epidemiologic risk assessment in populations exposed to catastrophic nuclear events and as a means of validating physical dosimetry in radiation workers. Application requires knowledge of the magnitude of uncertainty in the biological dose estimates and an understanding of potential statistical pitfalls arising from their use. This paper describes the statistical aspects of biological dosimetry in general and presents a detailed analysis in the specific case of dosimetry for risk assessment using stable chromosome aberration frequency. Biological dose estimates may be obtained from a dose-response curve, but negative estimates can result and adjustment must be made for regression bias due to imprecise estimation when the estimates are used in regression analyses. Posterior-mean estimates, derived as the mean of the distribution of true doses compatible with a given value of the biological endpoint, have several desirable properties: they are nonnegative, less sensitive to extreme skewness in the true dose distribution, and implicitly adjusted to avoid regression bias. The methods necessitate approximating the true-dose distribution in the population in which biological dosimetry is being applied, which calls for careful consideration of this distribution through other information. An important question addressed here is to what extent the methods are robust to misspecification of this distribution, because in many applications of biological dosimetry it cannot be characterized well. The findings suggest that dosimetry based solely on stable chromosome aberration frequency may be useful for population-based risk assessment

Biologically based multistage modeling of radiation effects

Energy Technology Data Exchange (ETDEWEB)

William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

2005-08-30

This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

Science.gov (United States)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

2007-01-01

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Developing point of care and high-throughput biological assays for determining absorbed radiation dose

International Nuclear Information System (INIS)

Joiner, Michael C.; Thomas, Robert A.; Grever, William E.; Smolinski, Joseph M.; Divine, George W.; Konski, Andre A.; Auner, Gregory W.; Tucker, James D.

2011-01-01

Background and purpose: Systems are being developed to assess radiation exposure based on leukocyte mRNA levels obtained by finger-stick sampling. The goal is to provide accurate detection of dose exposures up to 10 Gy for up to 1 week following exposure. We previously showed that specific mRNA sequences increase expression within an hour of exposure, and some genes continue to show elevated expression for at least 24 h. Full duration and dose-dependence of this persistence remain to be determined. In the present study, real-time quantitative PCR (qPCR) was used to determine changes in gene expression. qPCR can rapidly analyze small blood samples and could be adopted into a field-portable instrument that provides a radiation dose readout within 30 min. Materials and methods: From previous microarray analysis of 21,000 genes expressed in human lymphoblastoid cells 4 h post-irradiation (0–4 Gy), 118 genes were selected for evaluation by qPCR of gene expression in the leukocytes of human blood irradiated in vitro with doses of 0–10 Gy from a Co-60 gamma source at a dose rate of 30 cGy/min. Results: Blood from 20 normal healthy human donors yielded many mRNA sequences that could be used for radiation dosimetry. We observed four genes with large and persistent responses following exposure: ASTN2, CDKN1A, GADD45A, and GDF15. Five genes were identified as reliably non-responsive and were suitable for use as endogenous controls: DPM1, ITFG1, MAP4, PGK1, and SLC25A36; of these, ITFG1 was used for the analyses presented here. A significant dose-responsive increase in expression occurred for CDKN1A that was >16-fold at 10 Gy and 3-fold at 0.5 Gy compared to pre-irradiation values. Conclusions: These data show large, selective increases in mRNA transcript levels that persist for at least 48 h after single exposures between 0.5 and 10 Gy. Stable, non-responsive mRNA sequences for use as endogenous controls were also identified. These results indicate that following further

Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

Science.gov (United States)

Miron, S D; Astărăstoae, V

2014-01-01

Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered.

Development of Software for dose Records Data Base Access

International Nuclear Information System (INIS)

Amaro, M.

1990-01-01

The CIEMAT personal dose records are computerized in a Dosimetric Data Base whose primary purpose was the individual dose follow-up control and the data handling for epidemiological studies. Within the Data Base management scheme, software development to allow searching of individual dose records by external authorised users was undertaken. The report describes the software developed to allow authorised persons to visualize on screen a summary of the individual dose records from workers included in the Data Base. The report includes the User Guide for the authorised list of users and listings of codes and subroutines developed. (Author) 2 refs

Small-scale laser based electron accelerators for biology and medicine: a comparative study of the biological effectiveness

Science.gov (United States)

Labate, Luca; Andreassi, Maria Grazia; Baffigi, Federica; Basta, Giuseppina; Bizzarri, Ranieri; Borghini, Andrea; Candiano, Giuliana C.; Casarino, Carlo; Cresci, Monica; Di Martino, Fabio; Fulgentini, Lorenzo; Ghetti, Francesco; Gilardi, Maria Carla; Giulietti, Antonio; Köster, Petra; Lenci, Francesco; Levato, Tadzio; Oishi, Yuji; Russo, Giorgio; Sgarbossa, Antonella; Traino, Claudio; Gizzi, Leonida A.

2013-05-01

Laser-driven electron accelerators based on the Laser Wakefield Acceleration process has entered a mature phase to be considered as alternative devices to conventional radiofrequency linear accelerators used in medical applications. Before entering the medical practice, however, deep studies of the radiobiological effects of such short bunches as the ones produced by laser-driven accelerators have to be performed. Here we report on the setup, characterization and first test of a small-scale laser accelerator for radiobiology experiments. A brief description of the experimental setup will be given at first, followed by an overview of the electron bunch characterization, in particular in terms of dose delivered to the samples. Finally, the first results from the irradiation of biological samples will be briefly discussed.

Biological dosimetry in radiation accidents. Dose-response curve by chromosomal aberrations analysis

International Nuclear Information System (INIS)

Hadjidekova, V.; Hristova, R.; Atanasova, P.; Popova, L.; Stainova, A.; Bulanova, M.; Georgieva, I.; Vukov, M.

2005-01-01

The aim of this paper is to obtain a dose-response relationship for chromosomal aberrations induced in human lymphocytes after in vitro irradiation. Peripheral blood samples of 7 different donors were used. The blood irradiation was done with Cs137 gamma-rays at different doses: 0.0, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0 and 3.0 Gy. Lymphocyte cultures were established and maintain for 48 hours at 37 0 C in CO 2 incubator for chromosomal aberration analysis. The dose response relationship has been established based on dysenteric and ring chromosomes yield. The relationship can be described by the following equation: Y = 0.0274D + 0.0251 D 2 , where (Y) = dysenteric and ring chromosomes yield, (D) = radiation dose obtained. EXCEL software was established for calculation of the received dose by using this equation, as a whole body equivalent dose acute irradiation

Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality

International Nuclear Information System (INIS)

Ling, C. Clifton; Humm, John; Larson, Steven; Amols, Howard; Fuks, Zvi; Leibel, Steven; Koutcher, Jason A.

2000-01-01

Purpose: The goals of this study were to survey and summarize the advances in imaging that have potential applications in radiation oncology, and to explore the concept of integrating physical and biological conformality in multidimensional conformal radiotherapy (MD-CRT). Methods and Materials: The advances in three-dimensional conformal radiotherapy (3D-CRT) have greatly improved the physical conformality of treatment planning and delivery. The development of intensity-modulated radiotherapy (IMRT) has provided the 'dose painting' or 'dose sculpting' ability to further customize the delivered dose distribution. The improved capabilities of nuclear magnetic resonance imaging and spectroscopy, and of positron emission tomography, are beginning to provide physiological and functional information about the tumor and its surroundings. In addition, molecular imaging promises to reveal tumor biology at the genotype and phenotype level. These developments converge to provide significant opportunities for enhancing the success of radiotherapy. Results: The ability of IMRT to deliver nonuniform dose patterns by design brings to fore the question of how to 'dose paint' and 'dose sculpt', leading to the suggestion that 'biological' images may be of assistance. In contrast to the conventional radiological images that primarily provide anatomical information, biological images reveal metabolic, functional, physiological, genotypic, and phenotypic data. Important for radiotherapy, the new and noninvasive imaging methods may yield three-dimensional radiobiological information. Studies are urgently needed to identify genotypes and phenotypes that affect radiosensitivity, and to devise methods to image them noninvasively. Incremental to the concept of gross, clinical, and planning target volumes (GTV, CTV, and PTV), we propose the concept of 'biological target volume' (BTV) and hypothesize that BTV can be derived from biological images and that their use may incrementally improve

Biological dosimetry of X-rays by micronuclei study

International Nuclear Information System (INIS)

Gomez, E.; Silva, A.; Navlet, J.

1991-01-01

Biological dosimetry consists of estimating absorbed doses for people exposed to radiation by mean biological methods. Several indicators used are based in hematological, biochemical an cytogenetics data, although nowadays without doubt, the cytogenetic method is considered to be the most reliable, in this case, the study of micronuclei in peripheral blood lymphocytes cytokinetic blocked can be related to absorbed dose through an experimental calibration curve. An experimental dose-response curve, using micronuclei assay for X-rays at 250 kVp, 43,79 rads/min and temperature 37 degree celsius has been produced. Experimental data is fitted to model Y=c+ α D+β D 2 where. Y is the number micronuclei per cell and D the dose. the curve is compared with those produced elsewhere

Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

Science.gov (United States)

Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

2008-10-01

This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

Skull base chordomas: analysis of dose-response characteristics

International Nuclear Information System (INIS)

Niemierko, Andrzej; Terahara, Atsuro; Goitein, Michael

1997-01-01

Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the α level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate

Agent-based modelling in synthetic biology.

Science.gov (United States)

Gorochowski, Thomas E

2016-11-30

Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

Center of cancer systems biology second annual workshop--tumor metronomics: timing and dose level dynamics.

Science.gov (United States)

Hahnfeldt, Philip; Hlatky, Lynn; Klement, Giannoula Lakka

2013-05-15

Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized. ©2013 AACR.

The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

Science.gov (United States)

Wang, Jidong; Wang, Junjie; Liao, Anyan; Zhuang, Hongqing; Zhao, Yong

2009-08-01

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

Tritium biological effects and perspective of the biological study

International Nuclear Information System (INIS)

Komatsu, Kenshi

1998-01-01

Since tritium is an emitter of weak β-rays (5.7keV) and is able to bind to DNA, i.e., the most important genome component, the biological effects should be expected to be more profound than that of X-rays and γ-rays. When carcinogenesis, genetical effects and the detriments for fetus and embryo were used as a biological endpoint, most of tritium RBE (relative biological effectiveness) ranged from 1 to 2. The tritium risk in man could be calculated from these RBEs and γ-ray risk for human exposure, which are obtained mainly from the data on Atomic Bomb survivors. However, the exposure modality from environmental tritium should be a chronic irradiation with ultra low dose rate or a fractionated irradiation. We must estimate the tritium effect in man based on biological experiments alone, due to lack of such epidemiological data. Low dose rate experiment should be always accompanied by the statistical problem of data, since their biological effects are fairy low, and they should involve a possible repair system, such as adaptive response (or hormesis effect) and 'Kada effect' observed in bacteria. Here we discuss future works for the tritium assessment in man, such as (1) developing a high radiation sensitive assay system with rodent hybrid cells containing a single human chromosome and also (2) study on mammal DNA repair at molecular levels using a radiosensitive hereditary disease, Nijmegen Breakage Syndrome. (author)

Specification of carbon ion dose at the National Institute of Radiological Sciences (NIRS)

International Nuclear Information System (INIS)

Matsufuji, Naruhiro; Nakai, Tatsuaki; Kanematsu, Nobuyuki

2007-01-01

The clinical dose distributions of therapeutic carbon beams, currently used at National Institute of Radiological Sciences (NIRS) Heavy Ion Medical Accelerator in Chiba (HIMAC), are based on in-vitro Human Salivary Gland (HSG) cell survival response and clinical experience from fast neutron radiotherapy. Moderate radiosensitivity of HSG cells is expected to be a typical response of tumours to carbon beams. At first, the biological dose distribution is designed so as to cause a flat biological effect on HSG cells in the spread-out Bragg peak (SOBP) region. Then, the entire biological dose distribution is evenly raised in order to attain a RBE (relative biological effectiveness)=3.0 at a depth where dose-averaged LET (linear energy transfer) is 80 keV/μm. At that point, biological experiments have shown that carbon ions can be expected to have a biological effect identical to fast neutrons, which showed a clinical RBE of 3.0 for fast neutron radiotherapy at NIRS. The resulting clinical dose distribution in this approximation is not dependent on dose level, tumour type or fractionation scheme and thus reduces the unknown parameters in the analysis of the clinical results. The width SOBP and the clinical/physical dose at the center of SOBP specify the dose distribution. The clinical results analyzed in terms of tumor control probability (TCP) were found to show good agreement with the expected RBE value at higher TCP levels. The TCP analysis method was applied for the prospective dose estimation of hypofractionation. (author)

Study of dose effect relationship at low doses for non quantitative reactions of skin intestinal mucosa and lung

International Nuclear Information System (INIS)

Dutreix, J.; Wambersie, A.

1977-01-01

Most of the biological reactions observed in animal experiments or in clinical studies are non quantitative and they only allow assessing an inequality between the effects produced by different irradiations. The method used in non quantitative studies is actually based on the relative contribution of irreparable events and reparable to the cell killing. It provides for the cell population involved in non quantitative biological effects some data which can be expressed in term of a cell survival curve. Such data can be useful in Radiation therapy particularly for maximizing the difference between biological effects by a proper choice of the fraction size. The initial part of the cell survival curve, within the range of doses actually used appears to be a straight exponential. This should allow the extrapolation to very low doses in the range of interest to Radiation Protection

Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

International Nuclear Information System (INIS)

Terahara, Atsuro; Niemierko, Andrzej; Goitein, Michael; Finkelstein, Dianne; Hug, Eugen; Liebsch, Norbert; O'Farrell, Desmond; Lyons, Sue; Munzenrider, John

1999-01-01

models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD. Conclusion: This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume

Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Jones, Bleddyn; Cominos, Matilda; Dale, Roger G.

2003-01-01

Purpose: To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. Methods: The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. Results: The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low α/β ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high α/β ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Conclusion: Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors

Contribution of the modulation of intensity and the optimization to deliver a dose adapted to the biological heterogeneities

International Nuclear Information System (INIS)

Kubs, F.

2007-10-01

The recent progress in functional imaging by Positron Emission Tomography (TEP) opens new perspectives in the delineation of target volumes in radiotherapy. The functional data is major; we can intend to adapt the irradiation doses on the tumor activity (TA) and to perform a dose escalation. Our objectives were (i) to characterize the TEP threshold, by quantifying the uncertainties of the target volume contour according to the lesion size and the threshold contour level, (ii) to set up the geometry suited to perform a high-precision irradiation based on the TA, (iii) to estimate the dosimetric impact of this new protocol and (iv) to verify that dosimetry is perfectly distributed. Three original phantoms were specially created to satisfy the constraints met, as well as two virtual phantoms containing 3 dose levels (dose level 3 = TA). Our results showed the importance of the effect threshold-volume on the planning in radiotherapy. To use this irradiation method, the diameter of 1 cm for the third level was able to be reached. A dose escalation of 20 Gy was possible between the second (70 Gy) and the third level (90 Gy). The dosimetric impact estimated on two real cases was suitable - increase of COIN (conformal index) from 0.6 to 0.8 and decrease of NTCP (normal tissue complication probability) of a factor 5 -. In absolute and relative dosimetry, the clinical tolerances were respected. So all the treatment process, going from the diagnosis with the TEP to reveal the TA, to the patient treatment made beforehand on phantom, and going through the ballistic and the dose calculation, was estimated and validated according to our objective to adapt the irradiation to the biological heterogeneities. However such high doses should be carefully estimated before being prescribed clinically and progress is also expected in imaging, because the minimal size which we can irradiate is on the limit of the resolution TEP. (author)

Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

DEFF Research Database (Denmark)

Christiansen, E; Goldney, R D; Beautrai, A L

2011-01-01

BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

Epistemological problems in assessing cancer risks at low radiation doses

International Nuclear Information System (INIS)

Walinder, G.

1987-01-01

Historically, biology has not been subjected to any epistemological analysis as has been the case with mathematics and physics. Our knowledge of the effects in biological systems of various stimuli proves to be dualistic in a complementary (although not mutually exclusive) way, which bears resemblance to the knowledge of phenomena in quantum physics. The dualistic limbs of biological knowledge are the action of stimuli and the response of the exposed, biological system. With regard to radiogenic cancer, this corresponds to the action of the ionizations and the response of the exposed mammal to that action, respectively. The following conclusions can be drawn from the present analysis: Predictions as to radiogenic cancer seem often if not always to have neglected the response variability (variations in radiosensitivity) in individuals or among individuals in populations, i.e. the predictions have been based exclusively on radiation doses and exposure conditions. The exposed individual or population, however, must be considered an open statistical system, i.e. a system in which predictions as to the effect of an agent are only conditionally possible. The knowledge is inverse to the size of the dose or concentration of the active agent. On epistemological grounds, we can not gain knowledge about the carcinogenic capacity of very low (non-dominant) radiation doses. Based on the same principle, we can not predict cancer risks at very low (non-dominant) radiation doses merely on the basis of models, or otherwise interpolated or extrapolated high-dose effects, observed under special exposure conditions

The usefulness of metal markers for CTV-based dose prescription in high-dose-rate interstitial brachytherapy

International Nuclear Information System (INIS)

Yoshida, Ken; Mitomo, Masanori; Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Yoshida, Mineo

2002-01-01

We employ a clinical target volume (CTV)-based dose prescription for high-dose-rate (HDR) interstitial brachytherapy. However, it is not easy to define CTV and organs at risk (OAR) from X-ray film or CT scanning. To solve this problem, we have utilized metal markers since October 1999. Moreover, metal markers can help modify dose prescription. By regulating the doses to the metal markers, refining the dose prescription can easily be achieved. In this research, we investigated the usefulness of the metal markers. Between October 1999 and May 2001, 51 patients were implanted with metal markers at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Osaka National Hospital (ONH) and Sanda City Hospital (SCH). Forty-nine patients (head and neck: 32; pelvis: 11; soft tissue: 3; breast: 3) using metal markers were analyzed. During operation, we implanted 179 metal markers (49 patients) to CTV and 151 markers (26 patients) to OAR. At treatment planning, CTV was reconstructed judging from the metal markers, applicator position and operation records. Generally, we prescribed the tumoricidal dose to an isodose surface that covers CTV. We also planned to limit the doses to OAR lower than certain levels. The maximum normal tissue doses were decided 80%, 150%, 100%, 50% and 200% of the prescribed doses for the rectum, the urethra, the mandible, the skin and the large vessel, respectively. The doses to the metal markers using CTV-based dose prescription were generated. These were compared with the doses theoretically calculated with the Paris system. Treatment results were also investigated. The doses to the 158 metal markers (42 patients) for CTV were higher than ''tumoricidal dose''. In 7 patients, as a result of compromised dose prescription, 9 markers were lower than the tumoricidal dose. The other 12 markers (7%) were excluded from dose evaluation because they were judged as miss-implanted. The doses to the 142 metal markers (24 patients) for OAR were lower

Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation

International Nuclear Information System (INIS)

Kal, H.B.; Kempen-Harteveld, M.L. van; Heijenbrok-Kal, M.H.; Struikmans, H.

2006-01-01

Background and Purpose: Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimes were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity. Material and Methods: A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained. Results: RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease-free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values. Conclusion: 'More dose is better', provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses. (orig.)

Relationship between dose and risk, and assessment of carcinogenic risks associated with low doses of ionizing radiation

International Nuclear Information System (INIS)

Tubiana, M.; Aurengo, A.

2005-01-01

This report raises doubts on the validity of using LNT (linear no-threshold) relationship for evaluating the carcinogenic risk of low doses (< 100 mSv) and even more for very low doses (< 10 mSv). The LNT concept can be a useful pragmatic tool for assessing rules in radioprotection for doses above 10 mSv; however since it is not based on biological concepts of our current knowledge, it should not be used without precaution for assessing by extrapolation the risks associated with low and even more so, with very low doses (< 10 mSv), especially for benefit-risk assessments imposed on radiologists by the European directive 97-43. The biological mechanisms are different for doses lower than a few dozen mSv and for higher doses. The eventual risks in the dose range of radiological examinations (0.1 to 5 mSv, up to 20 mSv for some examinations) must be estimated taking into account radiobiological and experimental data. An empirical relationship which has been just validated for doses higher than 200 mSv may lead to an overestimation of risks (associated with doses one hundred fold lower), and this overestimation could discourage patients from undergoing useful examinations and introduce a bias in radioprotection measures against very low doses (< 10 mSv). Decision makers confronted with problems of radioactive waste or risk of contamination, should re-examine the methodology used for the evaluation of risks associated with very low doses and with doses delivered at a very low dose rate. This report confirms the inappropriateness of the collective dose concept to evaluate population irradiation risks

Biological Dosimetry of X-rays by micronuclei study

International Nuclear Information System (INIS)

Gomez, E.; Silva, A.; Navlet, J.

1991-01-01

Biological dosimetry consists of estimating absorbed doses for people exposed to radiation by mean biological methods. Several indicators used are based in haematological, biochemical an cytogenetics data, although nowadays without doubt, the cytogenetic method is considered to be the most reliable, in this case, the study of micronuclei in peripheral blood lymphocytes citokinetics blocked can be related to absorbed dose through an experimental calibration curve. An experimental dose-response curve, using micronuclei assay for X-rays at 250 kVp, 43,79 rads/min and temperature 37 degree centigree has been produced. Experimental data is fitted to model Y=C+ αD+BD''2 where Y is the number of micronuclei per cell and D the dose. The curve is compared with those produced elsewhere. (Author) 24 refs

Biological therapy in geriatric patients

International Nuclear Information System (INIS)

Mego, M.

2012-01-01

Targeted biological therapy, alone or in combination with conventional chemotherapy, make significant progress in the treatment of patients with malignancy. Its use as opposed to high-dose chemotherapy is not limited by age, nevertheless, we have relatively little knowledge of the toxicity and effectiveness in geriatric patients. Aim of this article is to give an overview of the biological effectiveness and toxicity of anticancer therapy in geriatric patients, based on published data. (author)

Testing the Capacity of the National Biological Dose Response Plan (NBDRP) EX40801

Science.gov (United States)

2009-11-01

Blood Collection All donors were volunteers that willingly responded to an advertising call for participation in a research proposal approved by...Scorers from the same laboratory are shown in the same colour . In Figure 2, the dose estimates based on QuickScan are shown. Figure 3 shows the doses

Relative biological effectiveness of 125I seeds for low-dose-rate irradiation of PANC-1

International Nuclear Information System (INIS)

Wang Jidong; Wang Junjie; Zhuang Hongqing; Liao Anyan; Zhao Yong

2008-01-01

Objective: To investigate the relative biological effectiveness(RBE) of National Model 6711 125 I seeds and the response patterns of PANC-1 exposed to 125 I seeds irradiation. Methods: PANC-1 cells in exponential growth were irradiated at initial dose rate of 2.59 cGy/h in vitro and exposed to 1, 2, 4, 6, 8 and 10 Gy. Meanwhile, the other part of cells were exposed to the same doses by 60 Co at dose rate of 2.21 Gy/min. After irradiation, the cells were stained by trypan blue to measure the cellular mortality rate and to compare the changes along with plating times of 12, 24, 48 and 72 h after 4 Gy. The colonies were counted to obtain the plating efficiencies by colony-forming assay and the cell surviving faction was calculated to plot cell survival curves, and RBE of 125 I seeds relative to 60 Co was determined. Results: The cell death rate for continuous low- dose-rate (LDR) irradiation by 125 I seeds was greater than 60 Co at the same doses above or equal to 4 Gy. After 4 Gy irradiation, the cellular mortality rates were increased with times. The difference was significant between 125 I seeds and 60 Co. The survival fractions of 125 I were lower than those of 60 Co, and the RBE of 125 I relative to 60 Co was determined to be 1.45. Conclusion: The cell-killing effects for continuous low-dose-rate (LDR) irradiation by 125 I seeds are greater than acute high-dose-rate of 60 Co. (authors)

Absorbed doses behind bones with MR image-based dose calculations for radiotherapy treatment planning.

Science.gov (United States)

Korhonen, Juha; Kapanen, Mika; Keyrilainen, Jani; Seppala, Tiina; Tuomikoski, Laura; Tenhunen, Mikko

2013-01-01

Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo-CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T(1)∕T(2)∗-weighted MR image intensity values. A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion-based pseudo-CT image and in a bulk density pseudo-CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms. The calculations revealed that the applied bulk density pseudo-CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion-based pseudo-CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter bones). This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus

Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

International Nuclear Information System (INIS)

Lumen, A; George, N I

2017-01-01

The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L

Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

Energy Technology Data Exchange (ETDEWEB)

Lumen, A, E-mail: Annie.Lumen@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-110, Jefferson, AR 72079 (United States); George, N I, E-mail: Nysia.George@fda.hhs.gov [Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-20, Jefferson, AR 72079 (United States)

2017-05-01

The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L.

Dose specification for radiation therapy: dose to water or dose to medium?

International Nuclear Information System (INIS)

Ma, C-M; Li Jinsheng

2011-01-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Time and dose in carcinogenesis

International Nuclear Information System (INIS)

Mayneord, W.V.; Clarke, R.H.

1978-05-01

Previous work on the implications of different forms of dose response relationships is extended to include time as a variable, not only in time of irradiation but also in the time of appearance of effects following irradiation. The forms of relationships for time distribution of tumours revealed experimentally for both radiation and chemical carcinogens are first considered. It appears that much data may be correlated in terms of a log-normal distribution of tumour yield following the insult. Further, it is noted, that there is evidence that the median time of tumour appearance may be a function of total dose received or even of dose rate for protracted exposure. Using numerical values of these parameters derived from the biological literature speculative studies have been made of the effects on dose response relationships of using a time distribution of tumour yield, considering both uniform irradiation and point sources. In addition the effects of using dose rate rather than dose to define the log-normal distribution to tumour appearance have been investigated. It is assumed that biological response is directly proportional to dose but that effect is distributed in time. From this linear assumption the appearance of non-linear dose response relationships and apparent thresholds are continually seen. Finally, both the importance of attempting analyses of biological data in terms of stochastic concepts and the need for biological data to test our hypotheses is emphasised. (author)

A comparison of physically and radiobiologically based optimization for IMRT

International Nuclear Information System (INIS)

Jones, Lois; Hoban, Peter

2002-01-01

Many optimization techniques for intensity modulated radiotherapy have now been developed. The majority of these techniques including all the commercial systems that are available are based on physical dose methods of assessment. Some techniques have also been based on radiobiological models. None of the radiobiological optimization techniques however have assessed the clinically realistic situation of considering both tumor and normal cells within the target volume. This study considers a ratio-based fluence optimizing technique to compare a dose-based optimization method described previously and two biologically based models. The biologically based methods use the values of equivalent uniform dose calculated for the tumor cells and integral biological effective dose for normal cells. The first biologically based method includes only tumor cells in the target volume while the second considers both tumor and normal cells in the target volume. All three methods achieve good conformation to the target volume. The biologically based optimization without the normal tissue in the target volume shows a high dose region in the center of the target volume while this is reduced when the normal tissues are also considered in the target volume. This effect occurs because the normal tissues in the target volume require the optimization to reduce the dose and therefore limit the maximum dose to that volume

Biological dosimetry in radiological protection: dose response curves elaboration for 60Co and 137Cs

International Nuclear Information System (INIS)

Silva, Marcia Augusta da

1997-01-01

Ionizing radiation sources for pacific uses are being extensively utilized by modern society and the applications of these sources have raised the probability of the occurrence of accidents. The accidental exposition to radiation creates a necessity of the development of methods to evaluate dose quantity. This data could be obtained by the measurement of damage caused by radiation in the exposed person. The radiation dose can be estimated in exposed persons through physical methods (physical dosimetry) but the biological methods can't be dispensed, and among them, the cytogenetic one that makes use of chromosome aberrations (dicentric and centric ring) formed in peripheral blood lymphocytes (PBL) exposed to ionizing radiation. This method correlates the frequency of radioinduced aberrations with the estimated absorbed dose, as in vitro as in vivo, which is called cytogenetic dosimetry. By the introduction of improved new techniques in culture, in the interpretation of aberrations in the different analysers of slides and by the adoption of different statistical programs to analyse the data, significant differences are observed among laboratories in dose-response curves (calibration curves). The estimation of absorbed dose utilizing other laboratory calibration curves may introduce some uncertainties, so the International Atomic Energy Agency (IAEA) advises that each laboratory elaborates your own dose-response curve for cytogenetic dosimetry. The results were obtained from peripheral blood lymphocytes of the healthy and no-smoking donors exposed to 60 Co and 137 Cs radiation, with dose rate of 5 cGy.min. -1 . Six points of dose were determined 20,50,100,200,300,400 cGy and the control not irradiated. The analysed aberrations were of chromosomic type, dicentric and centric ring. The dose response curve for dicentrics were obtained by frequencies weighted in liner-quadratic mathematic model and the equation resulted were for 60 Co: Y = (3 46 +- 2.14)10 -4 cGy -1 + (3

Usefulness and limits of biological dosimetry based on cytogenetic methods

International Nuclear Information System (INIS)

Leonard, A.; Rueff, J.; Gerber, G. B.; Leonard, E. D.

2005-01-01

Damage from occupational or accidental exposure to ionising radiation is often assessed by monitoring chromosome aberrations in peripheral blood lymphocytes, and these procedures have, in several cases, assisted physicians in the management of irradiated persons. Thereby, circulating lymphocytes, which are in the G0 stage of the cell cycle are stimulated with a mitogenic agent, usually phytohaemagglutinin, to replicate in vitro their DNA and enter cell division, and are then observed for abnormalities. Comparison with dose response relationships obtained in vitro allows an estimate of exposure based on scoring: - Unstable aberrations by the conventional, well-established analysis of metaphases for chromosome abnormalities or for micronuclei; - So-called stable aberrations by the classical G-banding (Giemsa-Stain-banding) technique or by the more recently developed fluorescent in situ hybridisation (FISH) method using fluorescent-labelled probes for centromeres and chromosomes. Three factors need to be considered in applying such biological dosimetry: (1) Radiation doses in the body are often inhomogeneous. A comparison of the distribution of the observed aberrations among with that expected from a normal poisson distribution can allow conclusions to be made with regard to the inhomogeneity of exposure by means of the so-called contaminated poisson distribution method; however, its application requires a sufficiently large number of aberrations, i.e. an exposure to a rather large dose at a high dose rate. (2) Exposure can occur at a low dose rate (e.g. from spread or lost radioactive sources) rendering a comparison with in vitro exposure hazardous. Dose-effect relationships of most aberrations that were scored, such as translocations, follow a square law. Repair intervening during exposure reduces the quadratic component with decreasing dose rate as exposure is spread over a longer period of time. No valid solution for this problem has yet been developed, although

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

PENERAPAN BLENDED-PROBLEM BASED LEARNING DALAM PEMBELAJARAN BIOLOGI

Directory of Open Access Journals (Sweden)

Samuel Agus Triyanto

2016-07-01

Biologi abad 21 merupakan integrasi dan mengintegrasikan kembali sub disiplin ilmu biologi, serta integrasi biologi dengan disiplin ilmu lain untuk mengatasi permasalahan sosial. Penelitian ini bertujuan untuk mengetahui penerapan Blended-Problem Based Learning, aktivitas belajar, dan respon siswa dalam pembelajaran biologi. Penelitian ini merupakan penelitian survei dengan pendekatan deskriptif kualitatif. Data hasil penelitian menunjukkan bahwa aktivitas positif siswa dalam pembelajaran memuaskan, sedangkan respon siswa baik terhadap pembelajaran. Berdasarkan hasil penelitian, disimpulkan bahwa Blended-Problem Based Learning dapat diterapkan dan diterima sebagai model dalam pembelajaran.

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd→Be) for normal tissues. Pt. 3

International Nuclear Information System (INIS)

Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R.; Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V.

1990-01-01

The effect of single and fractionated doses of fast neutrons (42 MeV d→Bc ) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133 Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 ± 0.94 for infinitely small X-ray doses per fraction. (author)

Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation

International Nuclear Information System (INIS)

Wang, Yan; Zhou, Jiliu; Zhang, Pei; An, Le; Ma, Guangkai; Kang, Jiayin; Shi, Feng; Shen, Dinggang; Wu, Xi; Lalush, David S; Lin, Weili

2016-01-01

Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures. (paper)

Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

Energy Technology Data Exchange (ETDEWEB)

Schneider, R.A.; Albertini, F.; Koch, T.; Ares, C.; Lomax, A.; Goitein, G. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; Vitolo, V. [Fondazione CNAO, Pavia (Italy); Hug, E.B. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; ProCure Proton Therapy Centers, New York, NY (United States)

2013-12-15

Purpose: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). Patients and methods: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81 %), sarcomas (16 %) and meningiom (3 %). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. Results: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm{sup 3}. A mean of 93.2 % of the PTV was covered by at least 90 % of the prescribed dose. SB volumes (cm{sup 3}) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5 = 0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of > 70 Gy (RBE), SB received > 50 and > 60 Gy (RBE) in only 61 and 54 % of patients, respectively. Mean SB volumes (cm{sup 3}) covered by different dose levels (Gy, RBE) were: V20 (n = 24): 45.1, V50 (n = 19): 17.7, V60 (n = 17): 7.6 and V70 (n = 12): 2.4. No acute toxicity {>=} grade 2 or late SB sequelae were observed. Conclusion: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology. (orig.)

Biological dosimetry of ionizing radiation by chromosomal aberration analysis

International Nuclear Information System (INIS)

Gonzalez-Castano, S.; Silva, A.; Navlet, J.

1990-01-01

Biological dosimetry consists of estimating absorbed doses for people exposed to radiation by mean biological methods. Several indicators used are based in haematological, biochemical, and cytogenetic data, although nowadays without doubt, the cytogenetic method is considered to be the most reliable. In this case, the study ol chromosomal aberrations, normally dicentric chromosomes, in peripheral lymphocytes can be related to absorbed dose through an experimental calibration curve. An experimental dose-response curve, using dicentric chromosomes analysis, X-rays at 300 kVp, 114 rad/min and temperature 37 degree celsius has been produced. Experimental data is fitted to model Y =α + β 1 D + β 2 D 2 , where Y is the number of dicentrics per cell and D the dose. The curve is compared with those produced elsewhere. (Author) 14 refs

Biological dosimetry of ionizing radiation by chromosomal aberration analysis

International Nuclear Information System (INIS)

Navlet Armenta, J.M.; Gonzalez, S.; Silva, A.

1990-01-01

Biological dosimetry consists of estimating absorbed doses for people exposed to radiation by mean biological methods. Several indicators used are based in haemathological, biochemical, and cytogenetic data, although nowadays without doubt, the cytogenetic method is considered to be the most reliable. In this case, the study of chromosomal aberrations, normally dicentric chromosomes, in peripheral lymphocytes can be related to absorbed dose through an experimental calibration curve. An experimental dose-response curve using dicentric chromosomes analysis, X-rays at 300 kVp, 114 rad/min and temperature 37 o C has been produced. Experimental data is fitted to model Y = α+β 1 D+β 2 D 2 , where Y is the number of dicentrics per cell and D the dose. The curve is compared with those produced elsewhere. (Author)

Dose estimation of heavy ion beam by microdosimetry. Examination of the method to estimate biological effect from physical measurement of radiation quality

International Nuclear Information System (INIS)

Kase, Yuki; Sakama, Makoto; Tsuzuki, Daigo; Abe, Kyoko; Saotome, Naoya; Matsufuji, Naruhiro; Kanai, Tatsuaki; Matsumoto, Kouki; Furusawa, Yoshiya

2007-01-01

The absorbed dose (AD) of heavy ion (HI) beam (here, carbon beam) in HI therapy (unit, EGy) (D st ) to exert the actual clinical effect is for the irradiation of tumors deep in the body and is thus estimated by AD corrected with the relative biological effectiveness (RBE) of clinical endpoint: i.e., the relation is expressed by the equation RBE=D st /D rad | same-effect (D rad is AD of the reference X-ray to yield the same effect as the HI used for the intended clinical endpoint). This paper describes the process of the estimation in the title with consideration of depth dependences of AD of HI in accordance to Bragg curve, and of biological AD as determined by colony assay of human salivary gland tumor cells: in NIRS, the desired AD in HI therapy is calculated by multiplying 1.5 to physically measured AD of HI at RBE 10% (10% survival of the cells). This factor has been obtained by microdosimetry of Heavy Ion Medical Accelerator in Chiba (HIMAC) ions in NIRS with a small spherical proportional counter (LET-1/2, Far West Technology) of the diameter 1.27 cm having the tissue equivalent plastic wall and chamber filled with 4.4 kPa of propane-based gas to make the tissue-equivalence size 1.0 μm diameter. The measuring principle is based on the microdosimetric kinetic model reported previously. The calculated dose is found to agree with AD in HI therapeutic planning within 10% fluctuation. (R.T.)

The role of dose inhomogeneity in biological models of dose response

International Nuclear Information System (INIS)

Crawford-Brown, D.J.

1989-01-01

The paper focuses on the semi-empirical functions proposed by NAS (1980), ICRP (1977), in which terms for initiation and cell killing appear. The extent is not to produce a new model of carcinogenesis, or to reanalyse existing epidemiological data, but to explore whether an existing extrapolation function (proposed by the NAS) can be shown to have coherent theoretical support, while at the same time reproducing (however reasonably) the features of epidemiological data. Attention is restricted to irradiation by high LET radiations such as alpha particles, which may produce large inhomogeneities in both emission density and dose in cellular populations. Particular interest is directed towards epidemiological studies of uranium miners (Hornung and Meinhardt, 1987) and persons injected with 224 Ra (Spiess and Mays, 1970), although the results of the radium dial studies are included since they are discussed in the NAS report. Both populations are characterized by large uncertainties in dose estimation (mean organ dose) and by highly inhomogeneous patterns of irradiation within a single organ (Arnold and Jee, 1959; Diel, 1978; Singh, Bennettee and Wrenn, 1987; Rowland and Marshall, 1959). (author)

The researches on the effects of low doses irradiation

International Nuclear Information System (INIS)

2009-02-01

All research conducted as part of 'Risc-Rad' and those conducted by actors in international programs on low doses allow progress in understanding mechanisms of carcinogenesis associated with irradiation. The data do not question the use in radiation protection, risk estimation models based on a linear increase of the risk with the dose of radiation. Nevertheless, they show that the nature of biological responses induced by low doses of radiation has differences with the responses induced by high doses of radiation. They also show the diversity of effects/dose relationships as the mechanism observed and the importance of genetic predisposition in the individual sensitivity to low doses of radiation. It is therefore essential to continue to bring new data to better understand the complex biological effects and their impact on the establishment of radiation protection standards. In addition, the results have often been at the cellular level. The diversity of responses induced by radiations is also a function of cell types observed, the aging of cells and tissue organization. It is essential to strengthen researches at the tissue and body level, involving in vitro and in vivo approaches while testing the hypothesis in epidemiology with a global approach to systems biology. Over the past four years, the collaboration between partners of 'Risc-Rad' using experimental biology approaches and those using mathematical modeling techniques aimed at developing a new model describing the carcinogenesis induced by low radiation doses. On an other hand, The High level expert group on European low dose risk research (H.L.E.G.) develop programmes in the area of low dose irradiation (Germany, Finland, France, Italy and United Kingdom). It proposed a structure of trans national government called M.E.L.O.D.I. ( multidisciplinary european low dose initiative). Its objective is to structure and integrate European research by gathering around a common programme of multidisciplinary

Proposal of a probabilistic dose-response model

International Nuclear Information System (INIS)

Barrachina, M.

1997-01-01

A biologically updated dose-response model is presented as an alternative to the linear-quadratic model currently in use for cancer risk assessment. The new model is based on the probability functions for misrepair and/or unrepair of DNA lesions, in terms of the radiation damage production rate in the cell (supposedly, a stem cell) and its repair-rate constant. The model makes use, interpreting it on the basis of misrepair probabilities, of the ''dose and dose-rate effectiveness factor'' of ICRP, and provides the way for a continuous extrapolation between the high and low dose-rate regions, ratifying the ''linear non-threshold hypothesis'' as the main option. Anyhow, the model throws some doubts about the additive property of the dose. (author)

The radioinduced membranes injuries as biological dose indicators: mechanisms of studies and practical applications; Les dommages membranaires radio-induits comme bio-indicateurs de dose: etudes des mecanismes et applications pratiques

Energy Technology Data Exchange (ETDEWEB)

Vincent-Genod, Lucie

2001-10-15

After an accidental overexposure, the assessment of the received dose in biological dosimetry is performed by a method based on the effects of irradiation on the DNA molecule. But this technique shows some limitations; therefore we tried to find new bio-sensors of radiation exposure. We have pointed out that membrane is a critical target of ionising radiation after an in vitro and in vivo overexposure. In vitro, these modifications were involved in the radio-induced apoptotic pathway. The measure of membrane fluidity allowed us to obtain an overall view of cellular membrane. Moreover, in vivo, by changing the lipid nutritional status of animals, our results displayed the important role played by membrane lipid composition in radio-induced membrane alterations. Besides, membrane effects were adjusted by the extracellular physiological control, and in particular by the damages on membrane fatty acid pattern. Finally, we have tested the use of membrane fluidity index as a bio-sensor of radiation exposure on in vivo models and blood samples from medical total body irradiated patients. The results achieved on animal models suggested that the membrane fluidity index was a bio-sensor of radiation exposure. Nevertheless, the observations realised on patients highlight that the effect of the first dose fraction of the radiotherapy treatment had some difficulties to be noticed. Indeed, the combined treatment: chemotherapy and radiotherapy disturbed the membrane fluidity index measures. To conclude, whereas this parameter was not a bio-sensor of irradiation exposure usable in biological dosimetry, it may allow us to assess the radio-induced damages and their cellular but also tissue impacts. (author)

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

Science.gov (United States)

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

2017-08-01

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

Investigation on thiosulfate-involved organics and nitrogen removal by a sulfur cycle-based biological wastewater treatment process.

Science.gov (United States)

Qian, Jin; Lu, Hui; Cui, Yanxiang; Wei, Li; Liu, Rulong; Chen, Guang-Hao

2015-02-01

Thiosulfate, as an intermediate of biological sulfate/sulfite reduction, can significantly improve nitrogen removal potential in a biological sulfur cycle-based process, namely the Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI(®)) process. However, the related thiosulfate bio-activities coupled with organics and nitrogen removal in wastewater treatment lacked detailed examinations and reports. In this study, S2O3(2-) transformation during biological SO4(2-)/SO3(2-) co-reduction coupled with organics removal as well as S2O3(2-) oxidation coupled with chemolithotrophic denitrification were extensively evaluated under different experimental conditions. Thiosulfate is produced from the co-reduction of sulfate and sulfite through biological pathway at an optimum pH of 7.5 for organics removal. And the produced S2O3(2-) may disproportionate to sulfide and sulfate during both biological S2O3(2-) reduction and oxidation most possibly carried out by Desulfovibrio-like species. Dosing the same amount of nitrate, pH was found to be the more direct factor influencing the denitritation activity than free nitrous acid (FNA) and the optimal pH for denitratation (7.0) and denitritation (8.0) activities were different. Spiking organics significantly improved both denitratation and denitritation activities while minimizing sulfide inhibition of NO3(-) reduction during thiosulfate-based denitrification. These findings in this study can improve the understanding of mechanisms of thiosulfate on organics and nitrogen removal in biological sulfur cycle-based wastewater treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation of spot scanning dose optimization and dose calculation for helium ions in Hyperion

DEFF Research Database (Denmark)

Fuchs, Hermann; Alber, Markus; Schreiner, Thomas

2015-01-01

PURPOSE: Helium ions ((4)He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed...... published so far. The advantage of (4)He seems to lie in the reduction of dose to surrounding tissue and to OARs. Nevertheless, additional biological experiments and treatment planning studies with larger patient numbers and more tumor indications are necessary to study the possible benefits of helium ion...

A method to combine three dimensional dose distributions for external beam and brachytherapy radiation treatments for gynecological neoplasms

International Nuclear Information System (INIS)

Narayana, V.; Sahijdak, W.M.; Orton, C.G.

1997-01-01

Purpose: Radiation treatment of gynecological neoplasms, such as cervical carcinoma, usually combines external radiation therapy with one or more intracavitary brachytherapy applications. Although the dose from external beam radiation therapy and brachytherapy can be calculated and displayed in 3D individually, the dose distributions are not combined. At most, combined point doses are calculated for select points using various time-dose models. In this study, we present a methodology to combine external beam and brachytherapy treatments for gynecological neoplasms. Material and Methods: Three dimensional bio-effect treatment planning to obtain complication probability has been outlined. CT scans of the patient's pelvis with the gynecological applicator in place are used to outline normal tissue and tumor volumes. 3D external beam and brachytherapy treatment plans are developed separately and an external beam dose matrix and a brachytherapy dose matrix was calculated. The dose in each voxel was assumed to be homogeneous. The physical dose in each voxel of the dose matrix was then converted into extrapolated response dose (ERD) based on the linear quadratic model that accounts for the dose per fraction, number of fractions, dose rate, and complete or incomplete repair of sublethal damage (time between fractions). The net biological dose delivered was obtained by summing the ERD grids from external beam and brachytherapy since there was complete repair of sublethal damage between external beam and brachytherapy treatments. The normal tissue complication probability and tumor control probability were obtained using the biological dose matrix based on the critical element model. Results: The outlined method of combining external beam and brachytherapy treatments was implemented on gynecological treatments using an applicator for brachytherapy treatments. Conclusion: Implementation of the biological dose calculation that combine different modalities is extremely useful

Similarity criterion analysis of dose-response curves in biological assay and radioimmunoassay of hormones

International Nuclear Information System (INIS)

Cristakou, H.D.

1983-01-01

The difficulties involved in the control of biological and radioimmunological assay systems, and in the maintenance of standard, as well as, the usual heterogeneity of assayed samples require some evidence of similarity between the dose-response curves obtained with the standard and the sample. Nowadays the parallelism test is used to provide such evidence. However, some indications of non-normal errors distribution, such as the presence of out layers, render the parallelism test both conceptually implausible and statistically inefficient. In such a manner we suggest the non-parametric 'frequencial' test as a more sounding option. (author)

US Subseabed Disposal Program radioecological data base: summaries of available radionuclide concentration factors and biological half-lives

International Nuclear Information System (INIS)

Gomez, L.S.; Marietta, M.G.; Jackson, D.W.

1984-01-01

The US Subseabed Disposal Program has compiled an extensive objective concentration factor and biological half-life data base from the international marine radioecological literature. A microcomputer-based data management system has been implemented to provide statistical and graphical summaries of these data. The data base is constructed in a manner which allows subsets to be sorted using a number of inter-study variables such as organism category, tissue/organ category, geographic location (for in situ studies), and several laboratory-related conditions (e.g., exposure time and exposure concentration). We discuss concentration factor data summaries for many elements. We also discuss summary material for biological half-life data. We discuss the results of our review with the estimates of mean concentration factors provided by the IAEA. It is proposed that this presentation scheme will enable those concerned with predictive assessment of radiation dose in the marine environment to make a more judicious selection of data for a given application. 7 references

Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator

International Nuclear Information System (INIS)

Brandom, W.F.; Bloom, A.D.; Bistline, R.W.; Saccomanno, G.

1978-01-01

Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239 Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10 -2 /100 cells for uranium miners and 90.6 X 10 -2 /100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)

Biological monitors for low levels of ionising radiation

International Nuclear Information System (INIS)

Mohankumar, M.N.; Jeevanram, R.K.

1995-01-01

The biological effects of high doses of ionising radiation are well understood and the methods of measurement of these doses well established. However the effects due to extremely low doses remain by and large uncertain. This is because of the fact that at such low doses no gross symptoms are seen. In fact, at these levels the occurrence of double strand breaks leading to the formation of chromosomal aberrations like dicentrics is rare and chances of mutation due to base damage are negligible. Hence neither chromosomal aberration studies nor mutational assays are useful for detecting doses of the order of a few milligray. Results of exhaustive work done by various laboratories indicate that below 20 mGy the chromosomal aberration technique based on scoring of dicentrics cannot distinguish between a linear or a threshold model. However indirect methods like unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs) appear to be promising for the detection of radiation exposures due to low levels of radiation. This report reviews the available literature on the biological effects of low levels of ionising radiation and highlights the merits and demerits of the various methods employed in the measurement of UDS and SCE. The phenomenon of radio-adaptive response (RAR) and its relation to DNA repair is also discussed. (author)

Future development of biological understanding of radiation protection: implications of nonstochastic effects

International Nuclear Information System (INIS)

Hahn, F.F.; McClellan, R.O.; Boecker, B.B.; Muggenburg, B.A.

1988-01-01

Radiation-protection standards are based on minimizing or preventing biological effects in exposed populations. Radiation-induced biological effects can be classified as stochastic--malignant and hereditary diseases for which the probability of an effect occurring is a function of dose without threshold--and nonstochastic--inflammatory and degenerative diseases for which the severity and frequency of the effect varies with the dose and for which a threshold is present. The current International Commission on Radiation Protection (ICRP) approach for setting limits for intakes of radionuclides by workers, which accounts for doses to significantly exposed organs of the body, is based on limitation of stochastic effects in most situations. When setting exposure limits, nonstochastic effects are generally considered to be unlikely at the limits for stochastic effects. In some situations, limits based on prevention of nonstochastic effects are lower than for stochastic effects. This review considers the threshold radiation doses for thyroid, bone, liver and lung and their relationship to the limits recommended by the ICRP and the cancer risks at the limits. This review indicates that the threshold dose for nonstochastic effects in thyroid and lung is much above the dose limit as advocated by ICRP. The threshold dose for nonstochastic effects in bone and liver is much closer to the dose limit, but protection from nonstochastic effects should still be afforded by the dose limits

Estimation of absorbed dose and its biological effects in subjects undergoing neuro interventional radiological procedures

International Nuclear Information System (INIS)

Basheerudeen, Safa Abdul Syed; Subramanian, Vinodhini; Venkatachalam, Perumal; Joseph, Santosh; Selvam, Paneer; Jose, M.T.; Annalakshmi, O.

2016-01-01

Radiological imaging has many applications due to its non-invasiveness, rapid diagnosis of life threatening diseases, and shorter hospital stay which benefit patients of all age groups. However, these procedures are complicated and time consuming, which use repeated imaging views and radiation, thereby increasing patient dose, and collective effective dose to the background at low doses. The effects of high dose radiation are well established. However, the effects of low dose exposure remain to be determined. Therefore, investigating the effect on medically exposed individuals is an alternative source to understand the low dose effects of radiation. The ESD (Entrance Surface Dose) was recorded using Lithium borate based TL dosimeters to measure the doses received by the head, neck and shoulder of the study subjects (n = 70) who underwent procedures like cerebral angiography, coiling, stenting and embolization

Model predictions and analysis of enhanced biological effectiveness at low dose rates

International Nuclear Information System (INIS)

Watt, D.E.; Sykes, C.E.; Younis, A.-R.S.

1988-01-01

A severe challenge to all models purporting to describe the biological effects of ionizing radiation has arisen with the discovery of two phenomena: the anomalous trend with dose rate of the frequency of neoplastic transformation of mammalian cells and the apparent excessive damaging power of electron-capture radionuclides when incorporated into cell nuclei. A new model is proposed which predicts and enables interpretation of these phenomena. Radiation effectiveness is found to be expressible absolutely in terms of the geometrical cross-sectional area of the radiosensitive sites. The duration of the irradiation, the mean free path for ionization, the influence of particles in the slowing-down spectrum perrtaining in the medium and two collective time factors determining the mean repair rate and the mean lifetime of unidentified reactive chemical species [pt

Radiation physics, biophysics, and radiation biology

International Nuclear Information System (INIS)

Hall, E.J.

1992-05-01

The following research programs from the Center for Radiological Research of Columbia University are described: Design and development of a new wall-less ultra miniature proportional counter for nanodosimetry; some recent measurements of ionization distributions for heavy ions at nanometer site sizes with a wall-less proportional counter; a calculation of exciton energies in periodic systems with helical symmetry: application to a hydrogen fluoride chain; electron energy-loss function in polynucleotide and the question of plasmon excitation; a non-parametric, microdosimetric-based approach to the evaluation of the biological effects of low doses of ionizing radiation; high-LET radiation risk assessment at medium doses; high-LET radiobiological effects: increased lesion severity or increased lesion proximity; photoneutrons generated by high energy medical linacs; the biological effectiveness of neutrons; implications for radiation protection; molecular characterization of oncogenes induced by neutrons; and the inverse dose-rate effect for oncogenic transformation by charged particles is LET dependent

Quantification of radiation-induced epilation in the pig: a biological indicator of radiation dose to the skin

International Nuclear Information System (INIS)

Sieber, V.K.; Wilkinson, J.; Aluri, G.R.; Bywaters, T.

1993-01-01

Epilation in the pig has been quantified following single exposures of X-rays in the range 1.0-25.0Gy. Hair loss was dose-dependent for exposures between 1.0 and 15.0 Gy and this response was linearly related to dose. No further increase in hair loss was observed for doses ≥ 15.0 Gy as 20-30% of the hairs remained. It was assumed that these hairs were not actively growing at the time of irradiation and did, therefore, not express damage. The ED 50 for the loss of ≥ 30% of hairs was 3.8 Gy whilst that for the loss of ≥ 50% of hairs was 6.8 Gy and for the loss of ≥ 67% of hairs was 12.5 Gy. There was ± 7% hair loss per Gy exposure for doses between 0.0 and 15.0 Gy. Quantification of hair loss provided a more sensitive assay than the use of visual scoring systems. Hair loss was detectable within 4 weeks of irradiation. The system is simple, non-invasive and appears to have considerable potential for use as a biological dosemeter. (Author)

Track structure and dose: Alternative conceptual bases for nuclear therapy

International Nuclear Information System (INIS)

Katz, R.

1987-01-01

As one departs from the island of radiation quality encompassing photons and electrons of initial energy from about 100 keV to about 10 MeV toward increasingly higher LET particle irradiations, and from relatively uniform to inherently non-uniform radiation fields, dose and LET become less useful indices of radiation effect. Isodose profiles are not isoeffect profiles. RBEs vary with end point, with the state of oxygenation, with cell line, with tissue identity and with dose, and are multiple valued functions of LET. Dose, microdose and LET lack the descrimination needed to predict biological end points. RBE calculations made from cellular radiosensitivity parameters are consistent with RBEs measured both in vitro and in vivo. For such calculations, we must know the spectrum of particles and particle energies making up a high LET radiation field. To sharpen the calculations and make them directly relevant to therapy, we need to evaluate radiosensitivity parameters for human tissues. Both physical and biological data are needed for radiobiology and radiotherapy. For the question of hazard evaluation, we need to know the relation between transformations in vitro and cancer production in vivo. Using the same model as was used earlier for cellular inactivations, we have fitted tentative radiosensitivity parameters to recent data for cell transformations. The model is consistent with both gamma ray and fission neutron measurements. But a wider range of irradiations is needed to test these results. Delta rays play an important role in heavy ion radiobiology, but we do not now know either the cross-sections for delta ray production or the radial deposition of their energy with sufficient precision or generality. But it is this, the radial dose deposition, which is the physical basis for the calculation of action cross-sections. Studies for radiobiology and radiotherapy should also include the response of different physical detectors to a range of radiations, especially

Doses due to tritium releases by NET - data base and relevant parameters on biological tritium behaviour

International Nuclear Information System (INIS)

Diabate, S.; Strack, S.

1990-12-01

This study gives an overview on the current knowledge about the behaviour of tritium in plants and in food chains in order to evaluate the ingestion pathway modelling of existing computer codes for dose estimations. The tritium uptake and retention by plants standing at the beginning of the food chains is described. The different chemical forms of tritium, which may be released into the atmosphere (HT, HTO and tritiated organics), and incorporation of tritium into organic material of plants are considered. Uptake and metabolism of tritiated compounds in animals and man are reviewed with particular respect to organically bound tritium and its significance for dose estimations. Some basic remarks on tritium toxicity are also included. Furthermore, a choice of computer codes for dose estimations due to chronic or accidental tritium releases has been compared with respect to the ingestion pathway. (orig.) [de

Biological dosimetry study in differentiated thyroid carcinoma patients treated with 131Iodine

International Nuclear Information System (INIS)

Vallerga, Maria Belen

2008-11-01

Biological Dosimetry allows individual dose assessments based on the effect produced by ionizing radiation on a given biological parameter. The current biological endpoint being scored is chromosomal aberrations, relying on a lymphocytes culture from the patient's blood. The measured yield of chromosome aberrations is referred to a calibration curve obtaining the whole body dose. Different scenarios of overexposure can be taken into account by modifying the calculations leading to the dose estimate. Differentiated Thyroid Carcinoma patients undergo thyroidectomy followed by internal radiotherapy with 131 I. The treatment's success entails the delivery of a lethal dose to the tumour within the maximum tolerable dose to a critical organ (blood doses over 2 Gy could lead to bone marrow depression). Currently, there is no established agreement for the selection of radioiodine dosage. Historically, the empiric approach, based on clinical and biochemical data, has been recommended. Nevertheless, this method may not be associated with optimal outcomes. On the other hand, the dosimetric approach attempts to determine the maximum allowable activity to be administered, establishing its biokinetics by a diagnostic 131 I study. The methodology may be modified to further individualized treatment, however it requires validation. Biological dosimetry provides an independent measure of radiotherapy effect, as such it might aid in the validation process. Nonetheless, biological dosimetry has traditionally been applied in cases of external and accidental overexposure to ionizing radiation. Accordingly, it is mandatory to assess its value in medical internal incorporations (main objective of the present study). The applied treatment strategy comprises whole body dose assessment by biological and internal dosimetry in order to administer a personalized therapeutic activity. Overall, 20 patients with differentiated thyroid carcinoma were included in the study. For biological dosimetry

A study on mice exposure dose for low-dose gamma-irradiation using glass dosimeter

Energy Technology Data Exchange (ETDEWEB)

Noh, Sung Jin; Kim, Hyo Jin; Kim, Hyun; Jeong, Dong Hyeok; Son, Tae Gen; Kim, Jung Ki; Yang, Kwang Mo; Kang, Yeong Rok [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Nam, Sang Hee [Dept. of Biomedical Engineering, Inje University, Gimhae (Korea, Republic of)

2015-12-15

The low dose radiation is done for a long period, thus researchers have to know the exact dose distribution for the irradiated mouse. This research has been conducted in order to find out methods in transmitting an exact dose to mouse in a mouse irradiation experiment carried out using {sup 137}C{sub s} irradiation equipment installed in the DIRAMS (Dongnam Institution of Radiological and Medical Sciences) research center. We developed a single mouse housing cage and shelf with adjustable geometric factors such as distance and angle from collimator. The measurement of irradiated dose showed a maximal 42% difference of absorbed dose from the desired dose in the conventional irradiation system, whereas only 6% difference of the absorbed dose was measured in the self-developed mouse apartment system. In addition, multi mice housing showed much difference of the absorbed dose in between head and body, compared to single mouse housing in the conventional irradiation system. This research may allow further research about biological effect assessment for the low dose irradiation using the self-developed mouse apartment to provide more exact doses which it tries to transmit, and to have more reliability for the biological analysis results.

Late effects of low doses and dose rates

International Nuclear Information System (INIS)

Paretzke, H.G.

1980-01-01

This paper outlines the spectrum of problems and approaches used in work on the derivation of quantitative prognoses of late effects in man of low doses and dose rates. The origins of principal problems encountered in radiation risks assessments, definitions and explanations of useful quantities, methods of deriving risk factors from biological and epidemiological data, and concepts of risk evaluation and problems of acceptance are individually discussed

Comparison of radiation doses using weight-based protocol and dose modulation techniques for patients undergoing biphasic abdominal computed tomography examinations

Directory of Open Access Journals (Sweden)

Livingstone Roshan

2009-01-01

Full Text Available Computed tomography (CT of the abdomen contributes a substantial amount of man-made radiation dose to patients and use of this modality is on the increase. This study intends to compare radiation dose and image quality using dose modulation techniques and weight- based protocol exposure parameters for biphasic abdominal CT. Using a six-slice CT scanner, a prospective study of 426 patients who underwent abdominal CT examinations was performed. Constant tube potentials of 90 kV and 120 kV were used for all arterial and portal venous phase respectively. The tube current-time product for weight-based protocol was optimized according to patient′s body weight; this was automatically selected in dose modulations. The effective dose using weight-based protocol, angular and z-axis dose modulation was 11.3 mSv, 9.5 mSv and 8.2 mSv respectively for the patient′s body weight ranging from 40 to 60 kg. For patients of body weights ranging 60 to 80 kg, the effective doses were 13.2 mSv, 11.2 mSv and 10.6 mSv respectively. The use of dose modulation technique resulted in a reduction of 16 to 28% in radiation dose with acceptable diagnostic accuracy in comparison to the use of weight-based protocol settings.

SU-E-P-47: Evaluation of Improvement of Esophagus Sparing in SBRT Lung Patients with Biologically Based IMRT Optimization

International Nuclear Information System (INIS)

Liang, X; Penagaricano, J; Paudel, N; Zhang, X; Morrill, S; Corry, P; Han, E; Hardee, M; Ratanatharathorn, V

2015-01-01

Purpose: To study the potential of improving esophageal sparing for stereotactic body radiation therapy (SBRT) lung cancer patients by using biological optimization (BO) compared to conventional dose-volume based optimization (DVO) in treatment planning. Methods: Three NSCLC patients (PTV (62.3cc, 65.1cc, and 125.1cc) adjacent to the heart) previously treated with SBRT were re-planned using Varian Eclipse TPS (V11) using DVO and BO. The prescription dose was 60 Gy in 5 fractions normalized to 95% of the PTV volume. Plans were evaluated by comparing esophageal maximum doses, PTV heterogeneity (HI= D5%/D95%), and Paddick’s conformity (CI) indices. Quality of the plans was assessed by clinically-used IMRT QA procedures. Results: By using BO, the maximum dose to the esophagus was decreased 1384 cGy (34.6%), 502 cGy (16.5%) and 532 cGy (16.2%) in patient 1, 2 and 3 respectively. The maximum doses to spinal cord and the doses to 1000 cc and 1500 cc of normal lung were comparable in both plans. The mean doses (Dmean-hrt) and doses to 15cc of the heart (V15-hrt) were comparable for patient 1 and 2. However for patient 3, with the largest PTV, Dmean-hrt and V15-hrt increased by 62.2 cGy (18.3%) and 549.9 cGy (24.9%) respectively for the BO plans. The mean target HI of BO plans (1.13) was inferior to the DVO plans (1.07). The same trend was also observed for mean CI in BO plans (0.77) versus DVO plans (0.83). The QA pass rates (3%, 3mm) were comparable for both plans. Conclusion: This study demonstrated that the use of biological models in treatment planning optimization can substantially improve esophageal sparing without compromising spinal cord and normal lung doses. However, for the large PTV case (125.1cc) we studied here, Dmean-hrt and V15-hrt increased substantially. The target HI and CI were inferior in the BO plans

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

Energy Technology Data Exchange (ETDEWEB)

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Jäkel, Oliver [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schlampp, Ingmar [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a

A TLD dose algorithm using artificial neural networks

International Nuclear Information System (INIS)

Moscovitch, M.; Rotunda, J.E.; Tawil, R.A.; Rathbone, B.A.

1995-01-01

An artificial neural network was designed and used to develop a dose algorithm for a multi-element thermoluminescence dosimeter (TLD). The neural network architecture is based on the concept of functional links network (FLN). Neural network is an information processing method inspired by the biological nervous system. A dose algorithm based on neural networks is fundamentally different as compared to conventional algorithms, as it has the capability to learn from its own experience. The neural network algorithm is shown the expected dose values (output) associated with given responses of a multi-element dosimeter (input) many times. The algorithm, being trained that way, eventually is capable to produce its own unique solution to similar (but not exactly the same) dose calculation problems. For personal dosimetry, the output consists of the desired dose components: deep dose, shallow dose and eye dose. The input consists of the TL data obtained from the readout of a multi-element dosimeter. The neural network approach was applied to the Harshaw Type 8825 TLD, and was shown to significantly improve the performance of this dosimeter, well within the U.S. accreditation requirements for personnel dosimeters

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

Energy Technology Data Exchange (ETDEWEB)

Pham, R; Sun, B; Zhao, T; Li, H; Yang, D; Grantham, K; Goddu, S; Santanam, L; Bradley, J; Mutic, S; Kandlakunta, P; Zhang, T [Washington University School of Medicine, Saint Louis, MO (United States)

2016-06-15

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculated on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.

Comparison of the predictions of the LQ and CRE models for normal tissue damage due to biologically targeted radiotherapy with exponentially decaying dose rates

International Nuclear Information System (INIS)

O'Donoghue, J.A.; West of Schotland Health Boards, Glasgow

1989-01-01

For biologically targeted radiotherapy organ dose rates may be complex functions of time, related to the biodistribution kinetics of the delivery vehicle and radiolabel. The simples situation is where dose rates are exponentially decaying functions of time. Two normal tissue isoeffect models enable the effects of exponentially decaying dose rates to be addressed. These are the extension of the linear-quadratic model and the cumulative radiation effect model. This communication will compare the predictions of these models. (author). 14 refs.; 1 fig

Biological monitors for low levels of ionising radiation

Energy Technology Data Exchange (ETDEWEB)

Mohankumar, M N; Jeevanram, R K [Safety Research and Health Physics Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India)

1996-12-31

The biological effects of high doses of ionising radiation are well understood and the methods of measurement of these doses well established. However the effects due to extremely low doses remain by and large uncertain. This is because of the fact that at such low doses no gross symptoms are seen. In fact, at these levels the occurrence of double strand breaks leading to the formation of chromosomal aberrations like dicentrics is rare and chances of mutation due to base damage are negligible. Hence neither chromosomal aberration studies nor mutational assays are useful for detecting doses of the order of a few milligray. Results of exhaustive work done by various laboratories indicate that below 20 mGy the chromosomal aberration technique based on scoring of dicentrics cannot distinguish between a linear or a threshold model. However indirect methods like unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs) appear to be promising for the detection of radiation exposures due to low levels of radiation. This report reviews the available literature on the biological effects of low levels of ionising radiation and highlights the merits and demerits of the various methods employed in the measurement of UDS and SCE. The phenomenon of radio-adaptive response (RAR) and its relation to DNA repair is also discussed. (author). 98 refs., 11 figs., 4 tabs.

Considerations on absorbed dose estimates based on different β-dose point kernels in internal dosimetry

International Nuclear Information System (INIS)

Uchida, Isao; Yamada, Yasuhiko; Yamashita, Takashi; Okigaki, Shigeyasu; Oyamada, Hiyoshimaru; Ito, Akira.

1995-01-01

In radiotherapy with radiopharmaceuticals, more accurate estimates of the three-dimensional (3-D) distribution of absorbed dose is important in specifying the activity to be administered to patients to deliver a prescribed absorbed dose to target volumes without exceeding the toxicity limit of normal tissues in the body. A calculation algorithm for the purpose has already been developed by the authors. An accurate 3-D distribution of absorbed dose based on the algorithm is given by convolution of the 3-D dose matrix for a unit cubic voxel containing unit cumulated activity, which is obtained by transforming a dose point kernel into a 3-D cubic dose matrix, with the 3-D cumulated activity distribution given by the same voxel size. However, beta-dose point kernels affecting accurate estimates of the 3-D absorbed dose distribution have been different among the investigators. The purpose of this study is to elucidate how different beta-dose point kernels in water influence on the estimates of the absorbed dose distribution due to the dose point kernel convolution method by the authors. Computer simulations were performed using the MIRD thyroid and lung phantoms under assumption of uniform activity distribution of 32 P. Using beta-dose point kernels derived from Monte Carlo simulations (EGS-4 or ACCEPT computer code), the differences among their point kernels gave little differences for the mean and maximum absorbed dose estimates for the MIRD phantoms used. In the estimates of mean and maximum absorbed doses calculated using different cubic voxel sizes (4x4x4 mm and 8x8x8 mm) for the MIRD thyroid phantom, the maximum absorbed doses for the 4x4x4 mm-voxel were estimated approximately 7% greater than the cases of the 8x8x8 mm-voxel. They were found in every beta-dose point kernel used in this study. On the other hand, the percentage difference of the mean absorbed doses in the both voxel sizes for each beta-dose point kernel was less than approximately 0.6%. (author)

Electron dose map inversion based on several algorithms

International Nuclear Information System (INIS)

Li Gui; Zheng Huaqing; Wu Yican; Fds Team

2010-01-01

The reconstruction to the electron dose map in radiation therapy was investigated by constructing the inversion model of electron dose map with different algorithms. The inversion model of electron dose map based on nonlinear programming was used, and this model was applied the penetration dose map to invert the total space one. The realization of this inversion model was by several inversion algorithms. The test results with seven samples show that except the NMinimize algorithm, which worked for just one sample, with great error,though,all the inversion algorithms could be realized to our inversion model rapidly and accurately. The Levenberg-Marquardt algorithm, having the greatest accuracy and speed, could be considered as the first choice in electron dose map inversion.Further tests show that more error would be created when the data close to the electron range was used (tail error). The tail error might be caused by the approximation of mean energy spectra, and this should be considered to improve the method. The time-saving and accurate algorithms could be used to achieve real-time dose map inversion. By selecting the best inversion algorithm, the clinical need in real-time dose verification can be satisfied. (authors)

TESS-based dose-response using pediatric clonidine exposures.

Science.gov (United States)

Benson, Blaine E; Spyker, Daniel A; Troutman, William G; Watson, William A

2006-06-01

The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. 3,458 single-substance clonidine exposures in children TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a "taste or lick" (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) microg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). The logistic model describing medical outcome (P TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.

Reconstruction of biological networks based on life science data integration.

Science.gov (United States)

Kormeier, Benjamin; Hippe, Klaus; Arrigo, Patrizio; Töpel, Thoralf; Janowski, Sebastian; Hofestädt, Ralf

2010-10-27

For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH--an integration toolkit for building life science data warehouses, CardioVINEdb--a information system for biological data in cardiovascular-disease and VANESA--a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

Accuracy and Radiation Dose of CT-Based Attenuation Correction for Small Animal PET: A Monte Carlo Simulation Study

International Nuclear Information System (INIS)

Yang, Ching-Ching; Chan, Kai-Chieh

2013-06-01

-Small animal PET allows qualitative assessment and quantitative measurement of biochemical processes in vivo, but the accuracy and reproducibility of imaging results can be affected by several parameters. The first aim of this study was to investigate the performance of different CT-based attenuation correction strategies and assess the resulting impact on PET images. The absorbed dose in different tissues caused by scanning procedures was also discussed to minimize biologic damage generated by radiation exposure due to PET/CT scanning. A small animal PET/CT system was modeled based on Monte Carlo simulation to generate imaging results and dose distribution. Three energy mapping methods, including the bilinear scaling method, the dual-energy method and the hybrid method which combines the kVp conversion and the dual-energy method, were investigated comparatively through assessing the accuracy of estimating linear attenuation coefficient at 511 keV and the bias introduced into PET quantification results due to CT-based attenuation correction. Our results showed that the hybrid method outperformed the bilinear scaling method, while the dual-energy method achieved the highest accuracy among the three energy mapping methods. Overall, the accuracy of PET quantification results have similar trend as that for the estimation of linear attenuation coefficients, whereas the differences between the three methods are more obvious in the estimation of linear attenuation coefficients than in the PET quantification results. With regards to radiation exposure from CT, the absorbed dose ranged between 7.29-45.58 mGy for 50-kVp scan and between 6.61-39.28 mGy for 80-kVp scan. For 18 F radioactivity concentration of 1.86x10 5 Bq/ml, the PET absorbed dose was around 24 cGy for tumor with a target-to-background ratio of 8. The radiation levels for CT scans are not lethal to the animal, but concurrent use of PET in longitudinal study can increase the risk of biological effects. The

Calculation of integrated biological response in brachytherapy

International Nuclear Information System (INIS)

Dale, Roger G.; Coles, Ian P.; Deehan, Charles; O'Donoghue, Joseph A.

1997-01-01

Purpose: To present analytical methods for calculating or estimating the integrated biological response in brachytherapy applications, and which allow for the presence of dose gradients. Methods and Materials: The approach uses linear-quadratic (LQ) formulations to identify an equivalent biologically effective dose (BED eq ) which, if applied to a specified tissue volume, would produce the same biological effect as that achieved by a given brachytherapy application. For simple geometrical cases, BED multiplying factors have been derived which allow the equivalent BED for tumors to be estimated from a single BED value calculated at a dose reference point. For more complex brachytherapy applications a voxel-by-voxel determination of the equivalent BED will be more accurate. Equations are derived which when incorporated into brachytherapy software would facilitate such a process. Results: At both high and low dose rates, the BEDs calculated at the dose reference point are shown to be lower than the true values by an amount which depends primarily on the magnitude of the prescribed dose; the BED multiplying factors are higher for smaller prescribed doses. The multiplying factors are less dependent on the assumed radiobiological parameters. In most clinical applications involving multiple sources, particularly those in multiplanar arrays, the multiplying factors are likely to be smaller than those derived here for single sources. The overall suggestion is that the radiobiological consequences of dose gradients in well-designed brachytherapy treatments, although important, may be less significant than is sometimes supposed. The modeling exercise also demonstrates that the integrated biological effect associated with fractionated high-dose-rate (FHDR) brachytherapy will usually be different from that for an 'equivalent' continuous low-dose-rate (CLDR) regime. For practical FHDR regimes involving relatively small numbers of fractions, the integrated biological effect to

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

Science.gov (United States)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

Microdosimetric approach for lung dose assessments

International Nuclear Information System (INIS)

Hofmann, W.; Steinhausler, F.; Pohl, E.; Bernroider, G.

1980-01-01

In the macroscopic region the term ''organ dose'' is related to an uniform energy deposition within a homogeneous biological target. Considering the lung, inhaled radioactive nuclides, however, show a significant non-uniform distribution pattern throughout the respiratory tract. For the calculation of deposition and clearance of inhaled alpha-emitting radionuclides within different regions of this organ, a detailed compartment model, based on the Weibel model A was developed. Since biological effects (e.g. lung cancer initiation) are primarily caused at the cellular level, the interaction of alpha particles with different types of cells of the lung tissue was studied. The basic approach is to superimpose alpha particle tracks on magnified images of randomly selected tissue slices, simulating alpha emitting sources. Particle tracks are generated by means of a specially developed computer program and used as input data for an on-line electronic image analyzer (Quantimet-720). Using adaptive pattern recognition methods the different cells in the lung tissue can be identified and their distribution within the whole organ determined. This microdosimetric method is applied to soluble radon decay products as well as to insoluble, highly localized, plutonium particles. For a defined microdistribution of alpha emitters, the resulting dose, integrated over all cellular dose values, is compared to the compartmental doses of the ICRP lung model. Furthermore this methodology is also applicable to other organs and tissues of the human body for dose calculations in practical health physics. (author)

Radiation dose response of normal lung assessed by Cone Beam CT - A potential tool for biologically adaptive radiation therapy

International Nuclear Information System (INIS)

Bertelsen, Anders; Schytte, Tine; Bentzen, Soren M.; Hansen, Olfred; Nielsen, Morten; Brink, Carsten

2011-01-01

Background: Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. Methods: A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. Results: A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. Conclusions: CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

Directory of Open Access Journals (Sweden)

Zhuang Hong-Qing

2009-01-01

Full Text Available Abstract Background To investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro. Methods The CL187 cell line was exposed to radiation of 60Coγ ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR and Raf under continuous low dose rate irradiation (CLDR and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence. Results The relative biological effect (RBE for 125I seeds compared with 60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%. P 2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change. Conclusion 125I seeds resulted in more effective inhibition than 60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

International Nuclear Information System (INIS)

Kuo, Hsiang-Chi; Liu, Wen-Shan; Wu, Andrew; Mah, Dennis; Chuang, Keh-Shih; Hong, Linda; Yaparpalvi, Ravi; Guha, Chandan; Kalnicki, Shalom

2010-01-01

To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages. Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF 2 ). There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment. Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation

Breast dose reduction for chest CT by modifying the scanning parameters based on the pre-scan size-specific dose estimate (SSDE)

Energy Technology Data Exchange (ETDEWEB)

Kidoh, Masafumi; Utsunomiya, Daisuke; Oda, Seitaro; Nakaura, Takeshi; Yuki, Hideaki; Hirata, Kenichiro; Namimoto, Tomohiro; Sakabe, Daisuke; Hatemura, Masahiro; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Faculty of Life Sciences, Honjo, Kumamoto (Japan); Funama, Yoshinori [Kumamoto University, Department of Medical Physics, Faculty of Life Sciences, Honjo, Kumamoto (Japan)

2017-06-15

To investigate the usefulness of modifying scanning parameters based on the size-specific dose estimate (SSDE) for a breast-dose reduction for chest CT. We scanned 26 women with a fixed volume CT dose index (CTDI{sub vol}) (15 mGy) and another 26 with a fixed SSDE (15 mGy) protocol (protocol 1 and 2, respectively). In protocol 2, tube current was calculated based on the patient habitus obtained on scout images. We compared the mean breast dose and the inter-patient breast dose variability and performed linear regression analysis of the breast dose and the body mass index (BMI) of the two protocols. The mean breast dose was about 35 % lower under protocol 2 than protocol 1 (10.9 mGy vs. 16.8 mGy, p < 0.01). The inter-patient breast dose variability was significantly lower under protocol 2 than 1 (1.2 mGy vs. 2.5 mGy, p < 0.01). We observed a moderate negative correlation between the breast dose and the BMI under protocol 1 (r = 0.43, p < 0.01); there was no significant correlation (r = 0.06, p = 0.35) under protocol 2. The SSDE-based protocol achieved a reduction in breast dose and in inter-patient breast dose variability. (orig.)

Therapeutic treatment plan optimization with probability density-based dose prescription

International Nuclear Information System (INIS)

Lian Jun; Cotrutz, Cristian; Xing Lei

2003-01-01

The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

International Nuclear Information System (INIS)

Bender, Edward T.

2012-01-01

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when compared the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.

submitter Dose prescription in carbon ion radiotherapy: How to compare two different RBE-weighted dose calculation systems

CERN Document Server

Molinelli, Silvia; Mairani, Andrea; Matsufuji, Naruhiro; Kanematsu, Nobuyuki; Inaniwa, Taku; Mirandola, Alfredo; Russo, Stefania; Mastella, Edoardo; Hasegawa, Azusa; Tsuji, Hiroshi; Yamada, Shigeru; Vischioni, Barbara; Vitolo, Viviana; Ferrari, Alfredo; Ciocca, Mario; Kamada, Tadashi; Tsujii, Hirohiko; Orecchia, Roberto; Fossati, Piero

2016-01-01

Background and purpose: In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose $(D_{RBE})$ calculation can lead to deviations in the physical dose $(D_{phy})$ delivered to the patient. Our aim is to reduce target $D_{phy}$ deviations by converting prescription dose values. Material and methods: Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6 Gy (RBE) to 4.6 Gy (RBE), according to the Japanese semi-empirical model. The $D_{phy}$ was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate $D_{RBE}$. Target median $D_{RBE}$ ratios between MC + LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected $D_{RBE}$. Results: The MC ...

Reconstruction of biological networks based on life science data integration

Directory of Open Access Journals (Sweden)

Kormeier Benjamin

2010-06-01

Full Text Available For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH - an integration toolkit for building life science data warehouses, CardioVINEdb - a information system for biological data in cardiovascular-disease and VANESA- a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

Science.gov (United States)

Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

2013-08-12

resistant to short-term high-dose irradiation. This discrepancy is reconcilable based on the differences in the experimental conditions. We are just beginning to understand the biological effects of long-term low-dose exposures in animals. Further research is necessary to accurately assess the possible biological effects of the accident.

The induction of a tumor suppressor gene (p53) expression by low-dose radiation and its biological meaning

International Nuclear Information System (INIS)

Ohnishi, Takeo

1997-01-01

I report the induced accumulation of wild-type p53 protein of a tumor suppressor gene within 12 h in various organs of rats exposed to X-ray irradiation at low doses (10-50 cGy). The levels of p53 in some organs of irradiated rats were increased about 2- to 3-fold in comparison with the basal p53 levels in non-irradiated rats. Differences in the levels of p53 induction after low-dose X-ray irradiation were observed among the small intestine, bone marrow, brain, liver, adrenal gland, spleen, hypophysis and skin. In contrast, there was no obvious accumulation of p53 protein in the testis and ovary. Thus, the induction of cellular p.53 accumulation by low-dose X-ray irradiation in rats seems to be organ-specific. I consider that cell type, and interactions with other signal transduction pathways of the hormone system, immune system and nervous system may contribute to the variable induction of p53 by low-dose X-ray irradiation. I discussed the induction of p53 by radiation and its biological meaning from an aspect of the defense system for radiation-induced cancer. (author)

Convolution-based estimation of organ dose in tube current modulated CT

Science.gov (United States)

Tian, Xiaoyu; Segars, W. Paul; Dixon, Robert L.; Samei, Ehsan

2016-05-01

Estimating organ dose for clinical patients requires accurate modeling of the patient anatomy and the dose field of the CT exam. The modeling of patient anatomy can be achieved using a library of representative computational phantoms (Samei et al 2014 Pediatr. Radiol. 44 460-7). The modeling of the dose field can be challenging for CT exams performed with a tube current modulation (TCM) technique. The purpose of this work was to effectively model the dose field for TCM exams using a convolution-based method. A framework was further proposed for prospective and retrospective organ dose estimation in clinical practice. The study included 60 adult patients (age range: 18-70 years, weight range: 60-180 kg). Patient-specific computational phantoms were generated based on patient CT image datasets. A previously validated Monte Carlo simulation program was used to model a clinical CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). A practical strategy was developed to achieve real-time organ dose estimation for a given clinical patient. CTDIvol-normalized organ dose coefficients ({{h}\\text{Organ}} ) under constant tube current were estimated and modeled as a function of patient size. Each clinical patient in the library was optimally matched to another computational phantom to obtain a representation of organ location/distribution. The patient organ distribution was convolved with a dose distribution profile to generate {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} values that quantified the regional dose field for each organ. The organ dose was estimated by multiplying {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} with the organ dose coefficients ({{h}\\text{Organ}} ). To validate the accuracy of this dose estimation technique, the organ dose of the original clinical patient was estimated using Monte Carlo program with TCM profiles explicitly modeled. The

A theoretical approach to the problem of dose-volume constraint estimation and their impact on the dose-volume histogram selection

International Nuclear Information System (INIS)

Schinkel, Colleen; Stavrev, Pavel; Stavreva, Nadia; Fallone, B. Gino

2006-01-01

This paper outlines a theoretical approach to the problem of estimating and choosing dose-volume constraints. Following this approach, a method of choosing dose-volume constraints based on biological criteria is proposed. This method is called ''reverse normal tissue complication probability (NTCP) mapping into dose-volume space'' and may be used as a general guidance to the problem of dose-volume constraint estimation. Dose-volume histograms (DVHs) are randomly simulated, and those resulting in clinically acceptable levels of complication, such as NTCP of 5±0.5%, are selected and averaged producing a mean DVH that is proven to result in the same level of NTCP. The points from the averaged DVH are proposed to serve as physical dose-volume constraints. The population-based critical volume and Lyman NTCP models with parameter sets taken from literature sources were used for the NTCP estimation. The impact of the prescribed value of the maximum dose to the organ, D max , on the averaged DVH and the dose-volume constraint points is investigated. Constraint points for 16 organs are calculated. The impact of the number of constraints to be fulfilled based on the likelihood that a DVH satisfying them will result in an acceptable NTCP is also investigated. It is theoretically proven that the radiation treatment optimization based on physical objective functions can sufficiently well restrict the dose to the organs at risk, resulting in sufficiently low NTCP values through the employment of several appropriate dose-volume constraints. At the same time, the pure physical approach to optimization is self-restrictive due to the preassignment of acceptable NTCP levels thus excluding possible better solutions to the problem

TESS-based dose-response using pediatric clonidine exposures

International Nuclear Information System (INIS)

Benson, Blaine E.; Spyker, Daniel A.; Troutman, William G.; Watson, William A.

2006-01-01

Objective: The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. Methods: 3458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a 'taste or lick' (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) μg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). Results: The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P 0.0000) and Certainty (P = 0.045). Conclusion: TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures

Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

Energy Technology Data Exchange (ETDEWEB)

Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl [Medical Physics Department, Centre of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland); Nesteruk, Marta [Faculty of Physics, University of Warsaw, Warsaw (Poland); Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich (Switzerland); Brzozowska, Beata [Faculty of Physics, University of Warsaw, Warsaw (Poland); Kukołowicz, Paweł F. [Medical Physics Department, Centre of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)

2017-04-01

The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared for 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

Science.gov (United States)

Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

Statistical analysis of MRI-only based dose planning

DEFF Research Database (Denmark)

Korsholm, M. E.; Waring, L. W.; Paulsen, Rasmus Reinhold

2012-01-01

. MRIonly based RT eliminates these errors and reduce the time and costs of a CT scan. The aim of this study is to investigate the dosimetric differences of a treatment plan when the dose calculation is based on MRI as compared to CT. Materials and Methods: Four diagnostic groups are investigated; 12...... as a clinically approved treatment plan. The treatment planning software is Eclipse v.10.0 (Varian Medical Systems). The dose calculation based on MRI data is evaluated in two different ways; a homogeneous density assigned MRI (MRI unit), where the entire body is assigned an HU equal to water and a heterogeneous...... density assigned MRI (MRI bulk) where in addition the CT segmented bone is transferred to the MRI and assigned an age dependent HU based on ICRU report 46. The CT based clinical treatment plan and structure set are registered to the corresponding MRI unit and MRI bulk. The body is outlined on both the MRI...

Radiation oncology - Linking technology and biology in the treatment of cancer

International Nuclear Information System (INIS)

Coleman, C. Norman

2002-01-01

Technical advances in radiation oncology including CT-simulation, 3D-conformal and intensity-modulated radiation therapy (IMRT) delivery techniques, and brachytherapy have allowed greater treatment precision and dose escalation. The ability to intensify treatment requires the identification of the critical targets within the treatment field, recognizing the unique biology of tumor, stroma and normal tissue. Precision is technology based while accuracy is biologically based. Therefore, the intensity of IMRT will undoubtedly mean an increase in both irradiation dose and the use of biological agents, the latter considered in the broadest sense. Radiation oncology has the potential and the opportunity to provide major contributions to the linkage between molecular and functional imaging, molecular profiling and novel therapeutics for the emerging molecular targets for cancer treatment. This process of 'credentialing' of molecular targets will require multi disciplinary imaging teams, clinicians and basic scientists. Future advances will depend on the appropriate integration of biology into the training of residents, continuing post graduate education, participation in innovative clinical research and commitment to the support of basic research as an essential component of the practice of radiation oncology

Calibration curve to establish the exposure dose at Co60 gamma radiation

International Nuclear Information System (INIS)

Guerrero C, C.; Brena V, M.

2000-01-01

The biological dosimetry is an adequate method for the dose determination in cases of overexposure to ionizing radiation or doubt of the dose obtained by physical methods. It is based in the aberrations analysis produced in the chromosomes. The behavior of leisure in chromosomes is of dose-response type and it has been generated curves in distinct laboratories. Next is presented the curve for gamma radiation produced in the National Institute of Nuclear Research (ININ) laboratory. (Author)

Monte carlo calculation of the neutron effective dose rate at the outer surface of the biological shield of HTR-10 reactor

International Nuclear Information System (INIS)

Remetti, Romolo; Andreoli, Giulio; Keshishian, Silvina

2012-01-01

Highlights: ► We deal with HTR-10, that is a helium-cooled graphite-moderated pebble bed reactor. ► We carried out Monte Carlo simulation of the core by MCNP5. ► Extensive use of MCNP5 variance reduction methods has been done. ► We calculated the trend of neutron flux within the biological shield. ► We calculated neutron effective dose at the outer surface of biological shield. - Abstract: Research on experimental reactors, such as HTR-10, provide useful data about potentialities of very high temperature gas-cooled reactors (VHTR). The latter is today rated as one of the six nuclear reactor types involved in the Generation-IV International Forum (GIF) Initiative. In this study, the MCNP5 code has been employed to evaluate the neutron radiation trend vs. the biological shield's thickness and to calculate the neutron effective dose rate at the outer surface. The reactor's geometry has been completely modeled by means of lattices and universes provided by MCNP, even though some approximations were required. Monte Carlo calculations have been performed by means of a simple PC and, as a consequence, in order to obtain acceptable run times, it was made an extensive recourse to variance reduction methods.

Gamma regularization based reconstruction for low dose CT

International Nuclear Information System (INIS)

Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

2015-01-01

Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l 0 -norm and l 1 -norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. (paper)

Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects.

Science.gov (United States)

Hoffmann, Aswin L; den Hertog, Dick; Siem, Alex Y D; Kaanders, Johannes H A M; Huizenga, Henk

2008-11-21

Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

Science.gov (United States)

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Bio-indicators for radiation dose assessment

International Nuclear Information System (INIS)

Trivedi, A.

1990-12-01

In nuclear facilities, such as Chalk River Laboratories, dose to the atomic radiation workers (ARWs) is assessed routinely by using physical dosimeters and bioassay procedures in accordance with regulatory recommendations. However, these procedures may be insufficient in some circumstances, e.g., in cases where the reading of the physical dosimeters is questioned, in cases of radiation accidents where the person(s) in question was not wearing a dosimeter, or in the event of a radiation emergency when an exposure above the dose limits is possible. The desirability of being able to assess radiation dose on the basis of radio-biological effects has prompted the Dosimetric Research Branch to investigate the suitability of biological devices and techniques that could be used for this purpose. Current biological dosimetry concepts suggest that there does not appear to be any bio-indicator that could reliably measure the very low doses that are routinely measured by the physical devices presently in use. Nonetheless, bio-indicators may be useful in providing valuable supplementary information in cases of unusual radiation exposures, such as when the estimated body doses are doubtful because of lack of proper physical measurements, or in cases where available results need to be confirmed for medical treatment plannings. This report evaluates the present state of biological dosimetry and, in particular, assesses the efficiency and limits of individual indicators. This has led to the recommendation of a few promising research areas that may result in the development of appropriate biological dosimeters for operational and emergency needs at Chalk River

Estimation of absorbed doses on the basis of cytogenetic methods

International Nuclear Information System (INIS)

Shevchenko, V.A.; Rubanovich, A.V.; Snigiryova, G.P.

1998-01-01

Long-term studies in the field of radiation cytogenetics have resulted in the discovery of relationship between induction of chromosome aberrations and the type of ionizing radiation, their intensity and dose. This has served as a basis of biological dosimetry as an area of application of the revealed relationship, and has been used in the practice to estimate absorbed doses in people exposed to emergency irradiation. The necessity of using the methods of biological dosimetry became most pressing in connection with the Chernobyl accident in 1986, as well as in connection with other radiation situations that occurred in nuclear industry of the former USSR. The materials presented in our works demonstrate the possibility of applying cytogenetic methods for assessing absorbed doses in populations of different regions exposed to radiation as a result of accidents at nuclear facilities (Chernobyl, the village Muslymovo on the Techa river, the Three Mile Island nuclear power station in the USA where an accident occurred in 1979). Fundamentally, new possibilities for retrospective dose assessment are provided by the FISH-method that permits the assessment of absorbed doses after several decades since the exposure occurred. In addition, the application of this method makes it possible to restore the dynamics of unstable chromosome aberrations (dicentrics and centric rings), which is important for further improvement of the method of biological dosimetry based on the analysis of unstable chromosome aberrations. The purpose of our presentation is a brief description of the cytogenetic methods used in biological dosimetry, consideration of statistical methods of data analysis and a description of concrete examples of their application. (J.P.N.)

Biology relevant to space radiation

International Nuclear Information System (INIS)

Fry, R.J.M.

1997-01-01

There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extended space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration

Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

Science.gov (United States)

Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2018-01-01

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

Low-dose CT image reconstruction using gain intervention-based dictionary learning

Science.gov (United States)

Pathak, Yadunath; Arya, K. V.; Tiwari, Shailendra

2018-05-01

Computed tomography (CT) approach is extensively utilized in clinical diagnoses. However, X-ray residue in human body may introduce somatic damage such as cancer. Owing to radiation risk, research has focused on the radiation exposure distributed to patients through CT investigations. Therefore, low-dose CT has become a significant research area. Many researchers have proposed different low-dose CT reconstruction techniques. But, these techniques suffer from various issues such as over smoothing, artifacts, noise, etc. Therefore, in this paper, we have proposed a novel integrated low-dose CT reconstruction technique. The proposed technique utilizes global dictionary-based statistical iterative reconstruction (GDSIR) and adaptive dictionary-based statistical iterative reconstruction (ADSIR)-based reconstruction techniques. In case the dictionary (D) is predetermined, then GDSIR can be used and if D is adaptively defined then ADSIR is appropriate choice. The gain intervention-based filter is also used as a post-processing technique for removing the artifacts from low-dose CT reconstructed images. Experiments have been done by considering the proposed and other low-dose CT reconstruction techniques on well-known benchmark CT images. Extensive experiments have shown that the proposed technique outperforms the available approaches.

Carbamazepine degradation by gamma irradiation coupled to biological treatment

Energy Technology Data Exchange (ETDEWEB)

Wang, Shizong [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Wang, Jianlong, E-mail: wangjl@tsinghua.edu.cn [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory of Radioactive Wastes Treatment, Tsinghua University, Beijing 100084 (China)

2017-01-05

Highlights: • Carbamazepine was removed by the combined gamma radiation and biodegradation. • The removal efficiency of carbamazepine increased with dose. • Irradiation could enhance the mineralization of carbamazepine significantly. • The combined irradiation and biodegradation was effective for carbamazepine removal. - Abstract: Carbamazepine is an emerging contaminant and resistant to biodegradation, which cannot be effectively removed by the conventional biological wastewater treatment processes. In this study, the combined gamma irradiation and biodegradation was employed to remove carbamazepine from wastewater. The effect of dose on the removal of carbamazepine was studied at different doses (300, 600 and 800 Gy). The results showed that the removal efficiency of carbamazepine increased with dose increasing during the irradiation process. The maximum removal efficiency was 99.8% at 800 Gy, while the removal efficiency of total organic carbon (TOC) was only 26.5%. The removal efficiency of TOC increased to 79.3% after the sequent biological treatment. In addition, several intermediates and organic acids were detected. The possible degradation pathway of carbamazepine during the integrated irradiation and biodegradation was proposed. Based on the overall analysis, the combined gamma irradiation and biological treatment process can be an alternative for removing the recalcitrant organic pollutants such as carbamazepine from wastewater.

Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Troya, M; Orive, G

2015-04-01

Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plants ecotoxicology. A case of low doses and multi pollutant exposure

Energy Technology Data Exchange (ETDEWEB)

Geras' Kin, S.; Kim, J.; Evseeva, T.; Oudalova, A.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

2004-07-01

In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic {gamma}-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

Energy Technology Data Exchange (ETDEWEB)

O' Neill, Peter [University of Oxford; Anderson, Jennifer [University of Oxford

2014-10-02

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

International Nuclear Information System (INIS)

Cucinotta, Francis A

2016-01-01

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

Energy Technology Data Exchange (ETDEWEB)

Cucinotta, Francis A [Univ. of Nevada, Las Vegas, NV (United States)

2016-09-01

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

Modelling normal tissue isoeffect distribution in conformal radiotherapy of glioblastoma provides an alternative dose escalation pattern through hypofractionation without reducing the total dose

International Nuclear Information System (INIS)

Mangel, L.; Skriba, Z.; Major, T.; Polgar, C.; Fodor, J.; Somogyi, A.; Nemeth, G.

2002-01-01

The purpose of this study was to prove that by using conformal external beam radiotherapy (RT) normal brain structures can be protected even when applying an alternative approach of biological dose escalation: hypofractionation (HOF) without total dose reduction (TDR). Traditional 2-dimensional (2D) and conformal 3-dimensional (3D) treatment plans were prepared for 10 gliomas representing the subanatomical sites of the supratentorial brain. Isoeffect distributions were generated by the biologically effective dose (BED) formula to analyse the effect of conventionally fractionated (CF) and HOF schedules on both the spatial biological dose distribution and biological dose-volume histograms. A comparison was made between 2D-CF (2.0 Gy/day) and 3D-HOF (2.5 Gy/day) regimens, applying the same 60 Gy total doses. Integral biologically effective dose (IBED) and volumes received biologically equivalent to a dose of 54 Gy or more (V-BED54) were calculated for the lower and upper brain stem as organs of risk. The IBED values were lower with the 3D-HOF than with the 2D-CF schedule in each tumour location, means 22.7±17.1 and 40.4±16.9 in Gy, respectively (p<0.0001). The V-BED54 values were also smaller or equal in 90% of the cases favouring the 3D-HOF scheme. The means were 2.7±4.8 ccm for 3D-HOF and 10.7±12.7 ccm for 2D-CF (p=0.0006). Our results suggest that with conformal RT, fraction size can gradually be increased. HOF radiotherapy regimens without TDR shorten the treatment time and seem to be an alternative way of dose escalation in the treatment of glioblastoma

Modelling normal tissue isoeffect distribution in conformal radiotherapy of glioblastoma provides an alternative dose escalation pattern through hypofractionation without reducing the total dose

Energy Technology Data Exchange (ETDEWEB)

Mangel, L.; Skriba, Z.; Major, T.; Polgar, C.; Fodor, J.; Somogyi, A.; Nemeth, G. [National Research Inst. for Radiobiology and Radiohygiene, Budapest (Hungary)

2002-04-01

The purpose of this study was to prove that by using conformal external beam radiotherapy (RT) normal brain structures can be protected even when applying an alternative approach of biological dose escalation: hypofractionation (HOF) without total dose reduction (TDR). Traditional 2-dimensional (2D) and conformal 3-dimensional (3D) treatment plans were prepared for 10 gliomas representing the subanatomical sites of the supratentorial brain. Isoeffect distributions were generated by the biologically effective dose (BED) formula to analyse the effect of conventionally fractionated (CF) and HOF schedules on both the spatial biological dose distribution and biological dose-volume histograms. A comparison was made between 2D-CF (2.0 Gy/day) and 3D-HOF (2.5 Gy/day) regimens, applying the same 60 Gy total doses. Integral biologically effective dose (IBED) and volumes received biologically equivalent to a dose of 54 Gy or more (V-BED54) were calculated for the lower and upper brain stem as organs of risk. The IBED values were lower with the 3D-HOF than with the 2D-CF schedule in each tumour location, means 22.7{+-}17.1 and 40.4{+-}16.9 in Gy, respectively (p<0.0001). The V-BED54 values were also smaller or equal in 90% of the cases favouring the 3D-HOF scheme. The means were 2.7{+-}4.8 ccm for 3D-HOF and 10.7{+-}12.7 ccm for 2D-CF (p=0.0006). Our results suggest that with conformal RT, fraction size can gradually be increased. HOF radiotherapy regimens without TDR shorten the treatment time and seem to be an alternative way of dose escalation in the treatment of glioblastoma.

Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

International Nuclear Information System (INIS)

Armpilia, C; Dale, R G; Sandilos, P; Vlachos, L

2006-01-01

This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BED eq ) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component

Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells, at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect.

Science.gov (United States)

Zanichelli, Fulvia; Capasso, Stefania; Cipollaro, Marilena; Pagnotta, Eleonora; Cartenì, Maria; Casale, Fiorina; Iori, Renato; Galderisi, Umberto

2012-04-01

Brassica vegetables are attracting a great deal of attention as healthy foods because of the fact that they contain substantial amounts of secondary metabolite glucosinolates that are converted into isothiocyanates, such as sulforaphane [(-)1-isothiocyanato-4R-(methylsulfinyl)-butane] (R-SFN), through the actions of chopping or chewing the vegetables. Several studies have analyzed the biological and molecular mechanisms of the anti-cancer activity of synthetic R,S-sulforaphane, which is thought to be a result of its antioxidant properties and its ability to inhibit histone deacetylase enzymes (HDAC). Few studies have addressed the possible antioxidant effects of R-SFN, which could protect cells from the free radical damage that strongly contribute to aging. Moreover, little is known about the effect of R-SFN on stem cells whose longevity is implicated in human aging. We evaluated the effects of R-SFN on the biology on human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, support hematopoiesis, and contribute to the homeostatic maintenance of many organs and tissues. Our investigation found evidence that low doses of R-SFN promote MSCs proliferation and protect them from apoptosis and senescence, while higher doses have a cytotoxic effect, leading to the induction of cell cycle arrest, programmed cell death and senescence. The beneficial effects of R-SFN may be ascribed to its antioxidant properties, which were observed when MSC cultures were incubated with low doses of R-SFN. Its cytotoxic effects, which were observed after treating MSCs with high doses of R-SFN, could be attributed to its HDAC inhibitory activity. In summary, we found that R-SFN, like many other dietary supplements, exhibits a hormetic behavior; it is able to induce biologically opposite effects at different doses.

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

Energy Technology Data Exchange (ETDEWEB)

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash; Feddock, Jonathan; Randall, Marcus [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky 40536 (United States)

2014-02-15

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescription doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

International Nuclear Information System (INIS)

Luo, Wei; Molloy, Janelle; Aryal, Prakash; Feddock, Jonathan; Randall, Marcus

2014-01-01

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescription doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F r : with resensitization, F n : without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F r ) and without (F n ) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F r /F n were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F r /F n were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F r /F n were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F r was 1.07/1.11 (rounded to 1.1), and the averaged value of F n was 1.75/1.18. F r of 1.1 has been applied to

Basic dose response of fluorescent screen-based portal imaging device

International Nuclear Information System (INIS)

Yeo, In Hwan; Yonannes, Yonas; Zhu, Yunping

1999-01-01

The purpose of this study is to investigate fundamental aspects of the dose response of fluorescent screen-based electronic portal imaging devices (EPIDs). We acquired scanned signal across portal planes as we varied the radiation that entered the EPID by changing the thickness and anatomy of the phantom as well as the air gap between the phantom and the EPID. In addition, we simulated the relative contribution of the scintillation light signal in the EPID system. We have shown that the dose profile across portal planes is a function of the air gap and phantom thickness. We have also found that depending on the density change within the phantom geometry, errors associated with dose response based on the EPID scan can be as high as 7%. We also found that scintillation light scattering within the EPID system is an important source of error. This study revealed and demonstrated fundamental characteristics of dose response of EPID, as relative to that of ion chambers. This study showed that EPID based on fluorescent screen cannot be an accurate dosimetry system

Monte Carlo-based dose reconstruction in a rat model for scattered ionizing radiation investigations.

Science.gov (United States)

Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Anna; Kolb, Bryan; Kovalchuk, Olga

2013-09-01

In radiation biology, rats are often irradiated, but the precise dose distributions are often lacking, particularly in areas that receive scatter radiation. We used a non-dedicated set of resources to calculate detailed dose distributions, including doses to peripheral organs well outside of the primary field, in common rat exposure settings. We conducted a detailed dose reconstruction in a rat through an analog to the conventional human treatment planning process. The process consisted of: (i) Characterizing source properties of an X-ray irradiator system, (ii) acquiring a computed tomography (CT) scan of a rat model, and (iii) using a Monte Carlo (MC) dose calculation engine to generate the dose distribution within the rat model. We considered cranial and liver irradiation scenarios where the rest of the body was protected by a lead shield. Organs of interest were the brain, liver and gonads. The study also included paired scenarios where the dose to adjacent, shielded rats was determined as a potential control for analysis of bystander effects. We established the precise doses and dose distributions delivered to the peripheral organs in single and paired rats. Mean doses to non-targeted organs in irradiated rats ranged from 0.03-0.1% of the reference platform dose. Mean doses to the adjacent rat peripheral organs were consistent to within 10% those of the directly irradiated rat. This work provided details of dose distributions in rat models under common irradiation conditions and established an effective scenario for delivering only scattered radiation consistent with that in a directly irradiated rat.

A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy

International Nuclear Information System (INIS)

Lahanas, M; Baltas, D; Zamboglou, N

2003-01-01

Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives

Bioeffect modeling and equieffective dose concepts in radiation oncology – Terminology, quantities and units

International Nuclear Information System (INIS)

Bentzen, Søren M.; Dörr, Wolfgang; Gahbauer, Reinhard; Howell, Roger W.; Joiner, Michael C.; Jones, Bleddyn; Jones, Dan T.L.; Kogel, Albert J. van der; Wambersie, André; Whitmore, Gordon

2012-01-01

The International Commission on Radiation Units and Measurements (ICRU) Report Committee on “Bioeffect Modeling and Biologically Equivalent Dose Concepts in Radiation Therapy” is currently developing a comprehensive and consistent framework for radiobiological effect modeling based on the equieffective dose, EQDX α/β , a concept encompassing BED and EQD2 as special cases.

The Implementation of Research-based Learning on Biology Seminar Course in Biology Education Study Program of FKIP UMRAH

Science.gov (United States)

Amelia, T.

2018-04-01

Biology Seminar is a course in Biology Education Study Program of Faculty of Teacher Training and Education University of Maritim Raja Ali Haji (FKIP UMRAH) that requires students to have the ability to apply scientific attitudes, perform scientific writing and undertake scientific publications on a small scale. One of the learning strategies that can drive the achievement of learning outcomes in this course is Research-Based Learning. Research-Based Learning principles are considered in accordance with learning outcomes in Biology Seminar courses and generally in accordance with the purpose of higher education. On this basis, this article which is derived from a qualitative research aims at describing Research-based Learning on Biology Seminar course. Based on a case study research, it was known that Research-Based Learning on Biology Seminar courses is applied through: designing learning activities around contemporary research issues; teaching research methods, techniques and skills explicitly within program; drawing on personal research in designing and teaching courses; building small-scale research activities into undergraduate assignment; and infusing teaching with the values of researchers.

Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

Science.gov (United States)

Azzam, Edouard

Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

SU-E-T-806: Very Fast GPU-Based IMPT Dose Computation

Energy Technology Data Exchange (ETDEWEB)

Sullivan, A; Brand, M [Mitsubishi Electric Research Lab, Cambridge, MA (United States)

2015-06-15

Purpose: Designing particle therapy treatment plans is a dosimetrist-in-the-loop optimization wherein the conflicting constraints of achieving a desired tumor dose distribution must be balanced against the need to minimize the dose to nearby OARs. IMPT introduces an additional, inner, numerical optimization step in which the dosimetrist’s current set of constraints are used to determine the weighting of beam spots. Very fast dose calculations are needed to enable the dosimetrist to perform many iterations of the outer optimization in a commercially reasonable time. Methods: We have developed a GPU-based convolution-type dose computation algorithm that more accurately handles heterogeneities than earlier algorithms by redistributing energy from dose computed in a water volume. The depth dependence of the beam size is handled by pre-processing Bragg curves using a weighted superposition of Gaussian bases. Additionally, scattering, the orientation of treatment ports, and the non-parallel propagation of beams are handled by large, but sparse, energy-redistribution matrices that implement affine transforms. Results: We tested our algorithm using a brain tumor dataset with 1 mm voxels and a single treatment port from the patient’s anterior through the sinuses. The resulting dose volume is 100 × 100 × 230 mm with 66,200 beam spots on a 3 × 3 × 2 mm grid. The dose computation takes <1 msec on a GeForce GTX Titan GPU with the Gamma passing rate for 2mm/2% criterion of 99.1% compared to dose calculated by an alternative dose algorithm based on pencil beams. We will present comparisons to Monte Carlo dose calculations. Conclusion: Our high-speed dose computation method enables the IMPT spot weights to be optimized in <1 second, resulting in a nearly instantaneous response to user changes to dose constraints. This permits the creation of higher quality plans by allowing the dosimetrist to evaluate more alternatives in a short period of time.

Optimizing CT radiation dose based on patient size and image quality: the size-specific dose estimate method

Energy Technology Data Exchange (ETDEWEB)

Larson, David B. [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States)

2014-10-15

The principle of ALARA (dose as low as reasonably achievable) calls for dose optimization rather than dose reduction, per se. Optimization of CT radiation dose is accomplished by producing images of acceptable diagnostic image quality using the lowest dose method available. Because it is image quality that constrains the dose, CT dose optimization is primarily a problem of image quality rather than radiation dose. Therefore, the primary focus in CT radiation dose optimization should be on image quality. However, no reliable direct measure of image quality has been developed for routine clinical practice. Until such measures become available, size-specific dose estimates (SSDE) can be used as a reasonable image-quality estimate. The SSDE method of radiation dose optimization for CT abdomen and pelvis consists of plotting SSDE for a sample of examinations as a function of patient size, establishing an SSDE threshold curve based on radiologists' assessment of image quality, and modifying protocols to consistently produce doses that are slightly above the threshold SSDE curve. Challenges in operationalizing CT radiation dose optimization include data gathering and monitoring, managing the complexities of the numerous protocols, scanners and operators, and understanding the relationship of the automated tube current modulation (ATCM) parameters to image quality. Because CT manufacturers currently maintain their ATCM algorithms as secret for proprietary reasons, prospective modeling of SSDE for patient populations is not possible without reverse engineering the ATCM algorithm and, hence, optimization by this method requires a trial-and-error approach. (orig.)

Study on the evaluation of radiation doses in dental radiography. Doses and risks due to dental full mouth examination

Energy Technology Data Exchange (ETDEWEB)

Sugimoto, K [Kanagawa Dental Coll., Yokosuka (Japan)

1980-09-01

Radiation doses and possible biological risks due to dental full mouth examination (adult: 10-film technique, child: 6-film technique) were evaluated based on preliminary experiments and statistical surveillance of patients' records. Dosimetrical studies were performed by using head and neck phantoms and a dental x-ray tube. Radiation doses were measured by x-ray films and thermoluminescence dosimeters. For the obtained doses of skin, eyes, thyroid gland and bone marrow, the biological risk of leukemia and thyroid cancer was discussed on the statistical basis of patients at Kanagawa Dental College Hospital. The major findings were as follows: The total number of patients who recieved full mouth x-ray examination at Kanagawa Dental College Hospital in 1978 was 1,099. The number of male patients was 382 (3,804 films) and that of female patients was 717 (7,138 films). In both sexes, the number of patients was the greatest in the group of 8 - 14 years of age. The collective doses of bone marrow due to full mouth 10-film examination performed at Kanagawa Dental College Hospital in 1978 were approximately 6.0 rad, which could induce leukemia with a probability of 1/8,000. The collective doses of thyroid gland were approximately 13 rad, which could induce lethal thyroid cancer with a probability of 1/15,000. The radiation dose due to the dental radiography for examination at Kanagawa Dental College Hospital was proved to be apparently below the level that could actually induce radiation injuries. But the collective radiation doses due to dental examination in Japan as a whole were approximately 8,000 times greater than that in Kanagawa Dental College Hospital.

Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study

NARCIS (Netherlands)

Aten, J.J.; Oudega, M.L.; van Exel, E.; Stek, M.L.; van Waarde, J.A.

2015-01-01

In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment

Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

International Nuclear Information System (INIS)

Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.

2004-01-01

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment

Verification by the FISH translocation assay of historic doses to Mayak workers from external gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Sotnik, Natalia V.; Azizova, Tamara V. [Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region (Russian Federation); Darroudi, Firouz [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); College of North Atlantic, Department of Health Science, Centre for Human Safety and Environmental Research, Doha (Qatar); Ainsbury, Elizabeth A.; Moquet, Jayne E.; Lloyd, David C.; Hone, Pat A.; Edwards, Alan A. [Public Health England, Chilton, Oxfordshire (United Kingdom); Fomina, Janna [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands)

2015-11-15

The aim of this study was to apply the fluorescence in situ hybridization (FISH) translocation assay in combination with chromosome painting of peripheral blood lymphocytes for retrospective biological dosimetry of Mayak nuclear power plant workers exposed chronically to external gamma radiation. These data were compared with physical dose estimates based on monitoring with badge dosimeters throughout each person's working life. Chromosome translocation yields for 94 workers of the Mayak production association were measured in three laboratories: Southern Urals Biophysics Institute, Leiden University Medical Center and the former Health Protection Agency of the UK (hereinafter Public Health England). The results of the study demonstrated that the FISH-based translocation assay in workers with prolonged (chronic) occupational gamma-ray exposure was a reliable biological dosimeter even many years after radiation exposure. Cytogenetic estimates of red bone marrow doses from external gamma rays were reasonably consistent with dose measurements based on film badge readings successfully validated in dosimetry system ''Doses-2005'' by FISH, within the bounds of the associated uncertainties. (orig.)

Thermodynamic basis for expressing dose logarithmically

International Nuclear Information System (INIS)

Waddell, William J.

2008-01-01

The current explanations for using a logarithmic scale for the dose of a chemical, administered to a biological system, have all been empirical. There is a fundamental, thermodynamic reason why a logarithmic scale must be used. The chemical potential is the effect that a chemical exerts on any system, including biological systems. The chemical potential of a chemical in any system is directly proportional to the logarithm of its activity or concentration. Lack of understanding of this concept and the consequent use of a linear scale for dose has led to misinterpretation of many biological experiments

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Energy Technology Data Exchange (ETDEWEB)

Lemos-Pinto, M.M.P.; Cadena, M.; Santos, N.; Fernandes, T.S.; Borges, E.; Amaral, A., E-mail: marcelazoo@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear

2015-10-15

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates. (author)

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator.

Science.gov (United States)

Lemos-Pinto, M M P; Cadena, M; Santos, N; Fernandes, T S; Borges, E; Amaral, A

2015-10-01

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.

The relative biological effectiveness of antiprotons

DEFF Research Database (Denmark)

Holzscheiter, Michael H.; Alsner, Jan; Bassler, Niels

2016-01-01

Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the re......Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase...... of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight. Materials and methods: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target...

Histological image classification using biologically interpretable shape-based features

International Nuclear Information System (INIS)

Kothari, Sonal; Phan, John H; Young, Andrew N; Wang, May D

2013-01-01

Automatic cancer diagnostic systems based on histological image classification are important for improving therapeutic decisions. Previous studies propose textural and morphological features for such systems. These features capture patterns in histological images that are useful for both cancer grading and subtyping. However, because many of these features lack a clear biological interpretation, pathologists may be reluctant to adopt these features for clinical diagnosis. We examine the utility of biologically interpretable shape-based features for classification of histological renal tumor images. Using Fourier shape descriptors, we extract shape-based features that capture the distribution of stain-enhanced cellular and tissue structures in each image and evaluate these features using a multi-class prediction model. We compare the predictive performance of the shape-based diagnostic model to that of traditional models, i.e., using textural, morphological and topological features. The shape-based model, with an average accuracy of 77%, outperforms or complements traditional models. We identify the most informative shapes for each renal tumor subtype from the top-selected features. Results suggest that these shapes are not only accurate diagnostic features, but also correlate with known biological characteristics of renal tumors. Shape-based analysis of histological renal tumor images accurately classifies disease subtypes and reveals biologically insightful discriminatory features. This method for shape-based analysis can be extended to other histological datasets to aid pathologists in diagnostic and therapeutic decisions

CT-based dose calculations and in vivo dosimetry for lung cancer treatment

International Nuclear Information System (INIS)

Essers, M.; Lanson, J.H.; Leunens, G.; Schnabel, T.; Mijnheer, B.J.

1995-01-01

Reliable CT-based dose calculations and dosimetric quality control are essential for the introduction of new conformal techniques for the treatment of lung cancer. The first aim of this study was therefore to check the accuracy of dose calculations based on CT-densities, using a simple inhomogeneity correction model, for lung cancer patients irradiated with an AP-PA treatment technique. Second, the use of diodes for absolute exit dose measurements and an Electronic Portal Imaging Device (EPID) for relative transmission dose verification was investigated for 22 and 12 patients, respectively. The measured dose values were compared with calculations performed using our 3-dimensional treatment planning system, using CT-densities or assuming the patient to be water-equivalent. Using water-equivalent calculations, the actual exit dose value under lung was, on average, underestimated by 30%, with an overall spread of 10% (1 SD). Using inhomogeneity corrections, the exit dose was, on average, overestimated by 4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due to the inhomogeneity correction model. An uncertainty in exit dose calculation of 2.5% (1 SD) could be explained by organ motion, resulting from the ventilatory or cardiac cycle. The most important reason for the large overall spread was, however, the uncertainty involved in performing point measurements: about 4% (1 SD). This difference resulted from the systematic and random deviation in patient set-up and therefore in diode position with respect to patient anatomy. Transmission and exit dose values agreed with an average difference of 1.1%. Transmission dose profiles also showed good agreement with calculated exit dose profiles. Our study shows that, for this treatment technique, the dose in the thorax region is quite accurately predicted using CT-based dose calculations, even if a simple inhomogeneity correction model is used. Point detectors such as diodes are not suitable for exit

Exposure to low doses of ionizing radiations

International Nuclear Information System (INIS)

Le Guen, B.

2008-01-01

The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

Low-dose ion-based transmission radiography and tomography for optimization of carbon ion-beam therapy

Energy Technology Data Exchange (ETDEWEB)

Magallanes Hernandez, Lorena

2017-02-21

In the last few decades, ion-beam radiotherapy has emerged as a highly effective tumor treatment modality. Its success relies on the capability to precisely confine the prescribed dose within the target volume, due to the inverted depth-dose profile and the finite range featured by charged particles. However, to fully exploit the physical and biological advantages of ion-beams, it is necessary to prioritize on innovative imaging techniques to monitor the ion-range inside the patient. Main range uncertainties result from X-ray-based calibration of the ion relative Water Equivalent Path Length (rWEPL) during the planning phase, and patient anatomical or positioning variation during the treatment. In this thesis, low-dose carbon-ion transmissionimaging performed with a Residual Range Detector (RRD) is proposed as imaging strategy for actively scanned beam delivery facilities. It enables the verification of the beam range and the patient positioning with ion-radiographies (iRAD), and ion computed tomographies (iCT) can directly provide the ion stopping-power of the traversed tissue for treatment planning purposes. First experimental investigations aiming to minimize the imaging dose to the object are presented. The performance of the integration-mode multi-channel array of 61 parallel-plate ionization chambers (PPICs), interleaved with 3 mm thickness PMMA slabs, was thoroughly investigated for low-fluence irradiation. This characterization has been pursued in terms of beam-monitoring performance at the Heidelberg Ion-beam Therapy Center (HIT, Heidelberg, Germany), RRD signal-to-noise ratio (SNR), RRD charge-collection efficiency and drift voltage applied to the PPICs. Pixel-wise metrics for signal quality evaluation based on specific channel-charge features have been developed to support the visual assessment of the acquired images. Phantoms of different complexity and tissue-equivalent composition were imaged with high (5000 primaries per raster-scanning point (RP

Low-dose ion-based transmission radiography and tomography for optimization of carbon ion-beam therapy

International Nuclear Information System (INIS)

Magallanes Hernandez, Lorena

2017-01-01

In the last few decades, ion-beam radiotherapy has emerged as a highly effective tumor treatment modality. Its success relies on the capability to precisely confine the prescribed dose within the target volume, due to the inverted depth-dose profile and the finite range featured by charged particles. However, to fully exploit the physical and biological advantages of ion-beams, it is necessary to prioritize on innovative imaging techniques to monitor the ion-range inside the patient. Main range uncertainties result from X-ray-based calibration of the ion relative Water Equivalent Path Length (rWEPL) during the planning phase, and patient anatomical or positioning variation during the treatment. In this thesis, low-dose carbon-ion transmissionimaging performed with a Residual Range Detector (RRD) is proposed as imaging strategy for actively scanned beam delivery facilities. It enables the verification of the beam range and the patient positioning with ion-radiographies (iRAD), and ion computed tomographies (iCT) can directly provide the ion stopping-power of the traversed tissue for treatment planning purposes. First experimental investigations aiming to minimize the imaging dose to the object are presented. The performance of the integration-mode multi-channel array of 61 parallel-plate ionization chambers (PPICs), interleaved with 3 mm thickness PMMA slabs, was thoroughly investigated for low-fluence irradiation. This characterization has been pursued in terms of beam-monitoring performance at the Heidelberg Ion-beam Therapy Center (HIT, Heidelberg, Germany), RRD signal-to-noise ratio (SNR), RRD charge-collection efficiency and drift voltage applied to the PPICs. Pixel-wise metrics for signal quality evaluation based on specific channel-charge features have been developed to support the visual assessment of the acquired images. Phantoms of different complexity and tissue-equivalent composition were imaged with high (5000 primaries per raster-scanning point (RP

Data base on nuclear power plant dose reduction research projects

Energy Technology Data Exchange (ETDEWEB)

Khan, T.A.; Baum, J.W.

1986-10-01

Staff at the ALARA Center of Brookhaven National Laboratory have established a data base of information about current research that is likely to result in lower radiation doses to workers. The data base, concerned primarily with nuclear power generation, is part of a project that the ALARA Center is carrying out for the Nuclear Regulatory Commission. This report describes its current status. A substantial amount of research on reducing occupational exposure is being done in the US and abroad. This research is beginning to have an impact on the collective dose expenditures at nuclear power plants. The collective radiation doses in Europe, Japan, and North America all show downward trends. A large part of the research in the US is either sponsored by the nuclear industry through joint industry organizations such as EPRI and ESEERCO or is done by individual corporations. There is also significant participation by smaller companies. The main emphasis of the research on dose reduction is on engineering approaches aimed at reducing radiation fields or keeping people out of high-exposure areas by using robotics. Effective ALARA programs are also underway at a large number of nuclear plants. Additional attention should be given to non-engineering approaches to dose reduction, which are potentially very useful and cost effective but require quantitative study and analysis based on data from nuclear power plants. 9 refs., 1 fig.

Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose-effect curve)

International Nuclear Information System (INIS)

Al-Achkar, W.

2001-09-01

In order to draw a dose-effect curve, experimentally gamma ray induced chromosomal aberrations in human peripheral lymphocytes from eight healthy people were studied. Samples from 4 males and 4 females were irradiated in tubes with 0.15, 0.25, 0.5, 1, 1.5, 2, 2.5 gray of gamma ray (Co 60 at dose rate 0.3 Gy/min). Irradiated and control samples were incubated in 37 centigrade for 48 hours cell cultures. Cell cultures then were stopped and metaphases spread, Giemsa stained to score the induced chromosomal aberrations. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics + rings and total numbers of breaks in cell for each individual or for all people were drawn. An increase of all chromosomal aberrations types with the elevation of the doses was observed. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

Physical and biological factors determining the effective proton range

International Nuclear Information System (INIS)

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Scholz, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita

2013-01-01

Purpose: Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods: Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results: Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions: The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

Science.gov (United States)

Kulka, Ulrike; Abend, Michael; Ainsbury, Elizabeth; Badie, Christophe; Barquinero, Joan Francesc; Barrios, Lleonard; Beinke, Christina; Bortolin, Emanuela; Cucu, Alexandra; De Amicis, Andrea; Domínguez, Inmaculada; Fattibene, Paola; Frøvig, Anne Marie; Gregoire, Eric; Guogyte, Kamile; Hadjidekova, Valeria; Jaworska, Alicja; Kriehuber, Ralf; Lindholm, Carita; Lloyd, David; Lumniczky, Katalin; Lyng, Fiona; Meschini, Roberta; Mörtl, Simone; Della Monaca, Sara; Monteiro Gil, Octávia; Montoro, Alegria; Moquet, Jayne; Moreno, Mercedes; Oestreicher, Ursula; Palitti, Fabrizio; Pantelias, Gabriel; Patrono, Clarice; Piqueret-Stephan, Laure; Port, Matthias; Prieto, María Jesus; Quintens, Roel; Ricoul, Michelle; Romm, Horst; Roy, Laurence; Sáfrány, Géza; Sabatier, Laure; Sebastià, Natividad; Sommer, Sylwester; Terzoudi, Georgia; Testa, Antonella; Thierens, Hubert; Turai, Istvan; Trompier, François; Valente, Marco; Vaz, Pedro; Voisin, Philippe; Vral, Anne; Woda, Clemens; Zafiropoulos, Demetre; Wojcik, Andrzej

2017-01-01

A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

Energy Technology Data Exchange (ETDEWEB)

Scott, Bobby, R., Ph.D.

2003-06-27

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

Science.gov (United States)

Davies, Robin; Hodge, Terrell; Enyedi, Alexander

2010-01-01

We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network. PMID:20810955

Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

Science.gov (United States)

Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

2010-01-01

We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

Measurement of radiation dose with a PC-based instrument