Dosimetric characteristics of fabricated silica fibre for postal radiotherapy dose audits

NASA Astrophysics Data System (ADS)

Fadzil, M. S. Ahmad; Ramli, N. N. H.; Jusoh, M. A.; Kadni, T.; Bradley, D. A.; Ung, N. M.; Suhairul, H.; Mohd Noor, N.

2014-11-01

Present investigation aims to establish the dosimetric characteristics of a novel fabricated flat fibre TLD system for postal radiotherapy dose audits. Various thermoluminescence (TL) properties have been investigated for five sizes of 6 mol% Ge-doped optical fibres. Key dosimetric characteristics including reproducibility, linearity, fading and energy dependence have been established. Irradiations were carried out using a linear accelerator (linac) and a Cobalt-60 machine. For doses from 0.5 Gy up to 10 Gy, Ge-doped flat fibres exhibit linearity between TL yield and dose, reproducible to better than 8% standard deviation (SD) following repeat measurements (n = 3). For photons generated at potentials from 1.25 MeV to 10 MV an energy-dependent response is noted, with a coefficient of variation (CV) of less than 40% over the range of energies investigated. For 6.0 mm length flat fibres 100 μm thick × 350 pm wide, the TL fading loss following 30 days of storage at room temperature was < 8%. The Ge-doped flat fibre system represents a viable basis for use in postal radiotherapy dose audits, corrections being made for the various factors influencing the TL yield.

Comparative dosimetric characterization for different types of detectors in high-energy electron beams

NASA Astrophysics Data System (ADS)

Lee, Chang Yeol; Kim, Woo Chul; Kim, Hun Jeong; Huh, Hyun Do; Park, Seungwoo; Choi, Sang Hyoun; Kim, Kum Bae; Min, Chul Kee; Kim, Seong Hoon; Shin, Dong Oh

2017-02-01

The purpose of this study is to perform a comparison and on analysis of measured dose factor values by using various commercially available high-energy electron beam detectors to measure dose profiles and energy property data. By analyzing the high-energy electron beam data from each detector, we determined the optimal detector for measuring electron beams in clinical applications. The dose linearity, dose-rate dependence, percentage depth dose, and dose profile of each detector were measured to evaluate the dosimetry characteristics of high-energy electron beams. The dose profile and the energy characteristics of high-energy electron beams were found to be different when measured by different detectors. Through comparison with other detectors based on the analyzed data, the microdiamond detector was found to have outstanding dose linearity, a low dose-rate dependency, and a small effective volume. Thus, this detector has outstanding spatial resolution and is the optimal detector for measuring electron beams. Radiation therapy results can be improved and related medical accidents can be prevented by using the procedure developed in this research in clinical practice for all beam detectors when measuring the electron beam dose.

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

PubMed

Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B; George, Kerry A; Cucinotta, Francis A

2016-01-01

The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

DOE PAGES

Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; ...

2016-04-25

The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictionsmore » of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Finally, we discuss comparisons of the resulting model parameters to those used in the NASA radiation quality factor function.« less

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.

The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictionsmore » of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Finally, we discuss comparisons of the resulting model parameters to those used in the NASA radiation quality factor function.« less

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

Total Ionizing Dose Effects in Bipolar and BiCMOS Devices

NASA Technical Reports Server (NTRS)

Chavez, Rosa M.; Rax, Bernard G.; Scheick, Leif Z.; Johnston, Allan H.

2005-01-01

This paper describes total ionizing dose (TID) test results performed at JPL. Bipolar and BiCMOS device samples were tested exhibiting significant degradation and failures at different irradiation levels. Linear technology which is susceptible to low-dose dependency (ELDRS) exhibited greater damage for devices tested under zero bias condition.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

PubMed

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2016-05-01

This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

A consistent two-mutation model of bone cancer for two data sets of radium-injected beagles.

PubMed

Bijwaard, H; Brugmans, M J P; Leenhouts, H P

2002-09-01

A two-mutation carcinogenesis model has been applied to model osteosarcoma incidence in two data sets of beagles injected with 226Ra. Taking age-specific retention into account, the following results have been obtained: (1) a consistent and well-fitting solution for all age and dose groups, (2) mutation rates that are linearly dependent on dose rate, with an exponential decrease for the second mutation at high dose rates, (3) a linear-quadratic dose-effect relationship, which indicates that care should be taken when extrapolating linearly, (4) highest cumulative incidences for injection at young adult age, and highest risks for injection doses of a few kBq kg(-1) at these ages, and (5) when scaled appropriately, the beagle model compares fairly well with a description for radium dial painters, suggesting that a consistent model description of bone cancer induction in beagles and humans may be possible.

Evaluation of linear array MOSFET detectors for in vivo dosimetry to measure rectal dose in HDR brachytherapy.

PubMed

Haughey, Aisling; Coalter, George; Mugabe, Koki

2011-09-01

The study aimed to assess the suitability of linear array metal oxide semiconductor field effect transistor detectors (MOSFETs) as in vivo dosimeters to measure rectal dose in high dose rate brachytherapy treatments. The MOSFET arrays were calibrated with an Ir192 source and phantom measurements were performed to check agreement with the treatment planning system. The angular dependence, linearity and constancy of the detectors were evaluated. For in vivo measurements two sites were investigated, transperineal needle implants for prostate cancer and Fletcher suites for cervical cancer. The MOSFETs were inserted into the patients' rectum in theatre inside a modified flatus tube. The patients were then CT scanned for treatment planning. Measured rectal doses during treatment were compared with point dose measurements predicted by the TPS. The MOSFETs were found to require individual calibration factors. The calibration was found to drift by approximately 1% ±0.8 per 500 mV accumulated and varies with distance from source due to energy dependence. In vivo results for prostate patients found only 33% of measured doses agreed with the TPS within ±10%. For cervix cases 42% of measured doses agreed with the TPS within ±10%, however of those not agreeing variations of up to 70% were observed. One of the most limiting factors in this study was found to be the inability to prevent the MOSFET moving internally between the time of CT and treatment. Due to the many uncertainties associated with MOSFETs including calibration drift, angular dependence and the inability to know their exact position at the time of treatment, we consider them to be unsuitable for in vivo dosimetry in rectum for HDR brachytherapy.

The feasibility assessment of radiation dose of movement 3D NIPAM gel by magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Hsieh, Chih-Ming; Leung, Joseph Hang; Ng, Yu-Bun; Cheng, Chih-Wu; Sun, Jung-Chang; Lin, Ping-Chin; Hsieh, Bor-Tsung

2015-11-01

NIPAM dosimeter is widely accepted and recommended for its 3D distribution and accuracy in dose absorption. Up to the moment, most research works on dose measurement are based on a fixed irradiation target without the consideration of the effect from physiological motion. We present a study to construct a respiratory motion simulating patient anatomical and dosimetry model for the study of dosimetic effect of organ motion. The dose on fixed and motion targets was measured by MRI after a dose adminstration of 1, 2, 5, 8, and 10 Gy from linear accelerator. Comparison of two situations is made. The average sensitivity of fixed NIPAM was 0.1356 s-1/Gy with linearity R2=0.998. The average sensitivity of movement NIPAM was 0.1366 s-1/Gy with linearity R2=0.998 both having only 0.001 of the sensitivity difference. The difference between the two based on dose rate dependency, position and depth was not significant. There was thus no apparent impact on NIPAM dosimeter from physiological motion. The high sensitivity, linearity and stability of NIPAM dosimeter proved to be an ideal apparatus in the dose measurement in these circumstances.

Effects of Alcohol on Performance on a Distraction Task During Simulated Driving

PubMed Central

Allen, Allyssa J.; Meda, Shashwath A.; Skudlarski, Pawel; Calhoun, Vince; Astur, Robert; Ruopp, Kathryn C.; Pearlson, Godfrey D.

2009-01-01

Background Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks. We studied this phenomenon, using a dual-task paradigm, involving performance of a visual oddball (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI (fMRI) studies of the VO task have shown activation in the anterior cingulate, hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases in activation of these areas during VO performance. Methods Forty healthy social drinkers were administered 3 different doses of alcohol, individually tailored to their gender and weight. Participants performed a VO task while operating a virtual reality driving simulator in a 3T fMRI scanner. Results Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance, primarily in hippocampus, anterior cingulate, and dorsolateral prefrontal areas, with the least activation occurring during the high dose. Behavioral analysis showed a dose-dependent linear increase in reaction time, with no effects associated with either correct hits or false alarms. In all dose conditions, driving speed decreased significantly after a VO stimulus. However, at the high dose this decrease was significantly less. Passenger-side line crossings significantly increased at the high dose. Conclusions These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions, which are involved with attentional processing/decision-making. Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving. PMID:19183133

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

Real-time dosimetry in radiotherapy using tailored optical fibers

NASA Astrophysics Data System (ADS)

Rahman, A. K. M. Mizanur; Zubair, H. T.; Begum, Mahfuza; Abdul-Rashid, H. A.; Yusoff, Z.; Omar, Nasr Y. M.; Ung, N. M.; Mat-Sharif, K. A.; Bradley, D. A.

2016-05-01

Real-time dosimetry plays an important role for accurate patient-dose measurement during radiotherapy. A tiny piece of laboratory fabricated Ge-doped optical fiber has been investigated as a radioluminescence (RL) sensor for real-time dosimetry over the dose range from 1 Gy to 8 Gy under 6 MV photon beam by LINAC. Fiber-coupled software-based RL prototype system was used to assess essential dosimetric characteristics including dose response linearity, dose rate dependency, sensitivity, repeatability and output dependence on field sizes. The consistency level of RL photon counts versus dose rate was also compared with that of standard Al2O3:C chips. Sensitivity of Ge-doped fiber were found to be sufficiently sensitive for practical use and also provided linear dose responses for various dose rates from 100 cGy/min to 600 cGy/min using both 6 MV photon and 6 MeV electron beams. SEM-EDX analysis was performed to identify Ge-dopant concentration level within the optical fiber RL material. Accumulated doses were also estimated using simple integral technique and the error was found to be around less than 1% under dissimilar dose rates or repeat measurements. The evaluation of the Ge-doped optical fiber based RL dosimeter system indicates its potential in medical dosimetry.

Characterization of the a-Si EPID in the unity MR-linac for dosimetric applications.

PubMed

Torres-Xirau, I; Olaciregui-Ruiz, I; Baldvinsson, G; Mijnheer, B J; van der Heide, U A; Mans, A

2018-01-09

Electronic portal imaging devices (EPIDs) are frequently used in external beam radiation therapy for dose verification purposes. The aim of this study was to investigate the dose-response characteristics of the EPID in the Unity MR-linac (Elekta AB, Stockholm, Sweden) relevant for dosimetric applications under clinical conditions. EPID images and ionization chamber (IC) measurements were used to study the effects of the magnetic field, the scatter generated in the MR housing reaching the EPID, and inhomogeneous attenuation from the MR housing. Dose linearity and dose rate dependencies were also determined. The magnetic field strength at EPID level did not exceed 10 mT, and dose linearity and dose rate dependencies proved to be comparable to that on a conventional linac. Profiles of fields, delivered with and without the magnetic field, were indistinguishable. The EPID center had an offset of 5.6 cm in the longitudinal direction, compared to the beam central axis, meaning that large fields in this direction will partially fall outside the detector area and not be suitable for verification. Beam attenuation by the MRI scanner and the table is gantry angle dependent, presenting a minimum attenuation of 67% relative to the 90° measurement. Repeatability, observed over two months, was within 0.5% (1 SD). In order to use the EPID for dosimetric applications in the MR-linac, challenges related to the EPID position, scatter from the MR housing, and the inhomogeneous, gantry angle-dependent attenuation of the beam will need to be solved.

Characterization of the a-Si EPID in the unity MR-linac for dosimetric applications

NASA Astrophysics Data System (ADS)

Torres-Xirau, I.; Olaciregui-Ruiz, I.; Baldvinsson, G.; Mijnheer, B. J.; van der Heide, U. A.; Mans, A.

2018-01-01

Electronic portal imaging devices (EPIDs) are frequently used in external beam radiation therapy for dose verification purposes. The aim of this study was to investigate the dose-response characteristics of the EPID in the Unity MR-linac (Elekta AB, Stockholm, Sweden) relevant for dosimetric applications under clinical conditions. EPID images and ionization chamber (IC) measurements were used to study the effects of the magnetic field, the scatter generated in the MR housing reaching the EPID, and inhomogeneous attenuation from the MR housing. Dose linearity and dose rate dependencies were also determined. The magnetic field strength at EPID level did not exceed 10 mT, and dose linearity and dose rate dependencies proved to be comparable to that on a conventional linac. Profiles of fields, delivered with and without the magnetic field, were indistinguishable. The EPID center had an offset of 5.6 cm in the longitudinal direction, compared to the beam central axis, meaning that large fields in this direction will partially fall outside the detector area and not be suitable for verification. Beam attenuation by the MRI scanner and the table is gantry angle dependent, presenting a minimum attenuation of 67% relative to the 90° measurement. Repeatability, observed over two months, was within 0.5% (1 SD). In order to use the EPID for dosimetric applications in the MR-linac, challenges related to the EPID position, scatter from the MR housing, and the inhomogeneous, gantry angle-dependent attenuation of the beam will need to be solved.

Performance of Al2O3:C optically stimulated luminescence dosimeters for clinical radiation therapy applications.

PubMed

Hu, B; Wang, Y; Zealey, W

2009-12-01

A commercial Optical Stimulated Luminescence (OSL) dosimetry system developed by Landauer was tested to analyse the possibility of using OSL dosimetry for external beam radiotherapy planning checks. Experiments were performed to determine signal sensitivity, dose response range, beam type/energy dependency, reproducibility and linearity. Optical annealing processes to test OSL material reusability were also studied. In each case the measurements were converted into absorbed dose. The experimental results show that OSL dosimetry provides a wide dose response range, good linearity and reproducibility for the doses up to 800cGy. The OSL output is linear with dose up to 600cGy range showing a maximum deviation from linearity of 2.0% for the doses above 600cGy. The standard deviation in response of 20 dosimeters was 3.0%. After optical annealing using incandescent light, the readout intensity decreased by approximately 98% in the first 30 minutes. The readout intensity, I, decreased after repeated optical annealing as a power law, given by I infinity t (-1.3). This study concludes that OSL dosimetry can provide an alternative dosimetry technique for use in in-vivo dosimetry if rigorous measurement protocols are established.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

González-López, Antonio, E-mail: antonio.gonzalez7@carm.es; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

Purpose: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Methods: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dosemore » ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. Results: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Conclusions: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.« less

Epiphytic lichenosynusia under conditions of chemical pollution: Dose-effect dependencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikhailova, I.N.; Vorobeichik, E.L.

1995-11-01

The dose-effect dependencies, which characterize response of the epiphytic lichenosynusia of southern taiga in the Middle Urals to pollution by discharges of a copper-smelting plant, are substantially non-linear and, in most cases, have an S-shaped form. A transition from background to impact state is very sharp and begins when the background level of pollution is exceeded by 1.5 - 2.3 times.

Characterization of a gated fiber-optic-coupled detector for application in clinical electron beam dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanyi, James A.; Nitzling, Kevin D.; Lodwick, Camille J.

2011-02-15

Purpose: Assessment of the fundamental dosimetric characteristics of a novel gated fiber-optic-coupled dosimetry system for clinical electron beam irradiation. Methods: The response of fiber-optic-coupled dosimetry system to clinical electron beam, with nominal energy range of 6-20 MeV, was evaluated for reproducibility, linearity, and output dependence on dose rate, dose per pulse, energy, and field size. The validity of the detector system's response was assessed in correspondence with a reference ionization chamber. Results: The fiber-optic-coupled dosimetry system showed little dependence to dose rate variations (coefficient of variation {+-}0.37%) and dose per pulse changes (with 0.54% of reference chamber measurements). The reproducibilitymore » of the system was {+-}0.55% for dose fractions of {approx}100 cGy. Energy dependence was within {+-}1.67% relative to the reference ionization chamber for the 6-20 MeV nominal electron beam energy range. The system exhibited excellent linear response (R{sup 2}=1.000) compared to reference ionization chamber in the dose range of 1-1000 cGy. The output factors were within {+-}0.54% of the corresponding reference ionization chamber measurements. Conclusions: The dosimetric properties of the gated fiber-optic-coupled dosimetry system compare favorably to the corresponding reference ionization chamber measurements and show considerable potential for applications in clinical electron beam radiotherapy.« less

Characteristics of an OSLD in the diagnostic energy range.

PubMed

Al-Senan, Rani M; Hatab, Mustapha R

2011-07-01

Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energy dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R2 > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 degrees in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.

Cataract production in mice by heavy charged particles

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Jose, U.; Yang, V. V.; Barker, M. E.

1981-01-01

The cataractogenic effects of heavy charged particles are evaluated in mice in relation to dose and ionization density. The relative biological effectiveness in relation to linear energy transfer for various particles is considered. Results indicated that low single doses (5 to 20 rad) of Fe 56 or Ar 40 particles are cataractogenic at 11 to 18 months after irradiation; onset and density of the opacification are dose related and cataract density (grade) at 9, 11, 13, and 16 months after irradiation shows partial linear energy transfer dependence. The severity of cataracts is reduced significantly when 417 rad of Co 60 gamma radiation is given in 24 weekly 17 rad fractions compared to giving this radiation as a single dose, but cataract severity is not reduced by fractionation of C12 doses over 24 weeks.

SU-E-T-159: Characteristics of Fiber-Optic Radiation Sensor for Proton Therapeutic Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, J; Kim, M; Hwang, U

Purpose: A fiber-optic radiation sensor using Cerenkov radiation has been widely studied for use as a dosimeter for proton therapeutic beam. Although the fiber-optic radiation sensor has already been investigated for proton therapeutic, it has been examined relatively little work for clinical therapeutic proton beams. In this study, we evaluated characteristics of a fiber-optic radiation sensor for clinical therapeutic proton beams. We experimentally evaluated dose-rate dependence, dose response and energy dependence for the proton beam. Methods: A fiber-optic radiation sensor was placed in a water phantom. Beams with energies of low, middle and high were used in the passively-scattered protonmore » therapeutic beam at the National Cancer Center in Korea. The sensor consists of two plastic optical fibers (POF). A reference POF and 2 cm longer POF were used to utilize the subtraction method for having sensitive volume. Each POF is optically coupled to the Multi-Anode Photo Multiplier Tube (MAPMT) and the MAPMT signals are processed using National Instruments Data Acquisition System (NI-DAQ). We were investigated dosimetric properties including dose-rate dependence, dose response and energy dependence. Results: We have successfully evaluated characteristics of a fiber optic radiation sensor using Cerenkov radiation. The fiber-optic radiation sensor showed the dose response linearity and low energy dependence. In addition, as the dose-rate was increased, Cerenkov radiation increased linearly. Conclusion: We evaluated the basic characteristics of the fiber optic radiation sensor, the dosimetry tool, to raise the quality of proton therapy. Based on the research, we developed a real time dosimetry system of the optic fiber to confirm the real time beam position and energy for therapeutic proton pencil beam.« less

Caffeine Increases the Linearity of the Visual BOLD Response

PubMed Central

Liu, Thomas T.; Liau, Joy

2009-01-01

Although the blood oxygenation level dependent (BOLD) signal used in most functional magnetic resonance imaging (fMRI) studies has been shown to exhibit nonlinear characteristics, most analyses assume that the BOLD signal responds in a linear fashion to stimulus. This assumption of linearity can lead to errors in the estimation of the BOLD response, especially for rapid event-related fMRI studies. In this study, we used a rapid event-related design and Volterra kernel analysis to assess the effect of a 200 mg oral dose of caffeine on the linearity of the visual BOLD response. The caffeine dose significantly (p < 0.02) increased the linearity of the BOLD response in a sample of 11 healthy volunteers studied on a 3 Tesla MRI system. In addition, the agreement between nonlinear and linear estimates of the hemodynamic response function was significantly increased (p= 0.013) with the caffeine dose. These findings indicate that differences in caffeine usage should be considered as a potential source of bias in the analysis of rapid event-related fMRI studies. PMID:19854278

Characterization of a prototype MR-compatible Delta4 QA system in a 1.5 tesla MR-linac

NASA Astrophysics Data System (ADS)

de Vries, J. H. W.; Seravalli, E.; Houweling, A. C.; Woodings, S. J.; van Rooij, R.; Wolthaus, J. W. H.; Lagendijk, J. J. W.; Raaymakers, B. W.

2018-01-01

To perform patient plan quality assurance (QA) on a newly installed MR-linac (MRL) it is necessary to have an MR-compatible QA device. An MR compatible device (MR-Delta4) has been developed together with Scandidos AB (Uppsala, Sweden). The basic characteristics of the detector response, such as short-term reproducibility, dose linearity, field size dependency, dose rate dependency, dose-per-pulse dependency and angular dependency, were investigated for the clinical Delta4-PT as well as for the MR compatible version. All tests were performed with both devices on a conventional linac and the MR compatible device was tested on the MRL as well. No statistically significant differences were found in the short-term reproducibility (<0.1%), dose linearity (⩽0.5%), field size dependency (<2.0% for field sizes larger than 5  ×  5 cm2), dose rate dependency (<1.0%) or angular dependency for any phantom/linac combination. The dose-per-pulse dependency (<0.8%) was found to be significantly different between the two devices. This difference can be explained by the fact that the diodes in the clinical Delta4-PT were irradiated with a much larger dose than the MR-Delta4-PT ones. The absolute difference between the devices (<0.5%) was found to be small, so no clinical impact is expected. For both devices, the results were consistent with the characteristics of the Delta4-PT device reported in the literature (Bedford et al 2009 Phys. Med. Biol. 54 N167-76 Sadagopan et al 2009 J. Appl. Clin. Med. Phys. 10 2928). We found that the characteristics of the MR compatible Delta4 phantom were found to be comparable to the clinically used one. Also, the found characteristics do not differ from the previously reported characteristics of the commercially available non-MR compatible Delta4-PT phantom. Therefore, the MR compatible Delta4 prototype was found to be safe and effective for use in the 1.5 tesla magnetic field of the Elekta MR-linac

Dosimetric characterization of a single crystal diamond detector in X-ray beams for preclinical research.

PubMed

Kampfer, Severin; Cho, Nathan; Combs, Stephanie E; Wilkens, Jan J

2018-05-29

The aim of this study was to investigate a single crystal diamond detector, the microDiamond detector from PTW (PTW-Freiburg, Freiburg, Germany), concerning the particular requirements in the set-up and energy range used in small animal radiotherapy (RT) research (around 220kV). We tested it to find out the minimal required pre-irradiation dose, the dose linearity, dose rate dependency and the angular response as well as usability in the small animal radiation research platform, SARRP (Xstrahl Ltd., Camberley, UK). For a stable signal in the range of energies used in the study, we found a required pre-irradiation dose of 10Gy. The dose linearity and dose rate dependence measurements showed a very good performance of the microDiamond detector. Regarding the effect of angular dependency, the variation of the response signal is less than 0.5% within the first 15° of the polar angle. In the azimuthal angle, however, there are differences in detector response up to 20%, depending on the range of energies used in the study. In addition, we compared the detector to a radiosensitive film for a profile measurement of a 5×5mm 2 irradiation field. Both methods showed a good accordance with the field size, however, the film has a steeper dose gradient in the penumbra region but also a higher noise than the microDiamond detector. We demonstrated that the microDiamond detector is a useful measurement tool for small animal RT research due to its small size. Nevertheless, it seems to be very important to verify the response of the detector in the given set-up and energy range. Copyright © 2018. Published by Elsevier GmbH.

High-temperature thermoluminescence of anion-deficient alumina and possibilities of its application in high-dose dosimetry

NASA Astrophysics Data System (ADS)

Surdo, A. I.; Milman, I. I.; Abashev, R. M.; Vlasov, M. I.

2014-12-01

Results of studies of the thermoluminescence (TL) of anion-deficient alumina (α-Al2O3 - δ) single crystals and based on them TLD-500 detectors exposed to pulsed X-ray and electron radiation in a wide range of doses D, pulsed dose rates P p , and temperatures are described. The TL responses of α-Al2O3 - δ for continuous and pulsed X-ray irradiation at D = 0.05-150 Gy are compared. Unlike continuous irradiation, in the case of pulsed irradiation at P p ≥ 6 × 106 Gy/s, a linear increase in the TL response as a function of D is registered in the main and "chromium" peaks at 450 and 580 K, respectively, with a decrease in the slope of the dose dependence at D > 2 Gy for the peak at 450 K. It is found that high-dose irradiation (>60 Gy) leads to the formation of a new TL peak at 830 K and the preferential redistribution of the stored light sums into this peak. The dose dependence for the TL peak at 830 K is studied. It is established that it is linear in a super-high dose range of 104 to 6 × 106 Gy at P p = 2.6 × 1011 Gy/s.

High dose-per-pulse electron beam dosimetry: Usability and dose-rate independence of EBT3 Gafchromic films.

PubMed

Jaccard, Maud; Petersson, Kristoffer; Buchillier, Thierry; Germond, Jean-François; Durán, Maria Teresa; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François O; Bailat, Claude

2017-02-01

The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate (Ḋ m ) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse (Ḋ p ) of up to 8 × 10 6 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response. Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 10 3 to 8 × 10 6 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates. We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 10 3 to 8 × 10 6 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse (D p ) measured by films and the charge per pulse (C p ) measured at the prototype linac exit. Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose-rate and energy independent. © 2016 American Association of Physicists in Medicine.

Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Nikjoo, H.; O'Neill, P.; Goodhead, D. T.

2000-01-01

PURPOSE: To investigate the role of kinetics in the processing of DNA double strand breaks (DSB), and the formation of simple chromosome exchange aberrations following X-ray exposures to mammalian cells based on an enzymatic approach. METHODS: Using computer simulations based on a biochemical approach, rate-equations that describe the processing of DSB through the formation of a DNA-enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simple exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting to experimental data. RESULTS: When mediated by a DSB repair enzyme complex, the processing of single DSB showed a complex behaviour that gives the appearance of fast and slow components of rejoining. This is due to the time-delay caused by the action time of enzymes in biomolecular reactions. It is shown that the kinetic- and dose-responses of simple chromosome exchange aberrations are well described by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition between two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear quadratic model. CONCLUSIONS: Using a minimal number of assumptions, the kinetics and dose response observed experimentally for DSB rejoining and the formation of simple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete for DSB repair.

Linear energy transfer in water phantom within SHIELD-HIT transport code

NASA Astrophysics Data System (ADS)

Ergun, A.; Sobolevsky, N.; Botvina, A. S.; Buyukcizmeci, N.; Latysheva, L.; Ogul, R.

2017-02-01

The effect of irradiation in tissue is important in hadron therapy for the dose measurement and treatment planning. This biological effect is defined by an equivalent dose H which depends on the Linear Energy Transfer (LET). Usually, H can be expressed in terms of the absorbed dose D and the quality factor K of the radiation under consideration. In literature, various types of transport codes have been used for modeling and simulation of the interaction of the beams of protons and heavier ions with tissue-equivalent materials. In this presentation we used SHIELD-HIT code to simulate decomposition of the absorbed dose by LET in water for 16O beams. A more detailed description of capabilities of the SHIELD-HIT code can be found in the literature.

Properties of a commercial PTW-60019 synthetic diamond detector for the dosimetry of small radiotherapy beams.

PubMed

Lárraga-Gutiérrez, José Manuel; Ballesteros-Zebadúa, Paola; Rodríguez-Ponce, Miguel; García-Garduño, Olivia Amanda; de la Cruz, Olga Olinca Galván

2015-01-21

A CVD based radiation detector has recently become commercially available from the manufacturer PTW-Freiburg (Germany). This detector has a sensitive volume of 0.004 mm(3), a nominal sensitivity of 1 nC Gy(-1) and operates at 0 V. Unlike natural diamond based detectors, the CVD diamond detector reports a low dose rate dependence. The dosimetric properties investigated in this work were dose rate, angular dependence and detector sensitivity and linearity. Also, percentage depth dose, off-axis dose profiles and total scatter ratios were measured and compared against equivalent measurements performed with a stereotactic diode. A Monte Carlo simulation was carried out to estimate the CVD small beam correction factors for a 6 MV photon beam. The small beam correction factors were compared with those obtained from stereotactic diode and ionization chambers in the same irradiation conditions The experimental measurements were performed in 6 and 15 MV photon beams with the following square field sizes: 10 × 10, 5 × 5, 4 × 4, 3 × 3, 2 × 2, 1.5 × 1.5, 1 × 1 and 0.5 × 0.5 cm. The CVD detector showed an excellent signal stability (<0.2%) and linearity, negligible dose rate dependence (<0.2%) and lower response angular dependence. The percentage depth dose and off-axis dose profiles measurements were comparable (within 1%) to the measurements performed with ionization chamber and diode in both conventional and small radiotherapy beams. For the 0.5 × 0.5 cm, the measurements performed with the CVD detector showed a partial volume effect for all the dosimetric quantities measured. The Monte Carlo simulation showed that the small beam correction factors were close to unity (within 1.0%) for field sizes ≥1 cm. The synthetic diamond detector had high linearity, low angular and negligible dose rate dependence, and its response was energy independent within 1% for field sizes from 1.0 to 5.0 cm. This work provides new data showing the performance of the CVD detector compared against a high spatial resolution diode. It also presents a comparison of the CVD small beam correction factors with those of diode and ionization chamber for a 6 MV photon beam.

In vivo proton dosimetry using a MOSFET detector in an anthropomorphic phantom with tissue inhomogeneity.

PubMed

Kohno, Ryosuke; Hotta, Kenji; Matsubara, Kana; Nishioka, Shie; Matsuura, Taeko; Kawashima, Mitsuhiko

2012-03-08

When in vivo proton dosimetry is performed with a metal-oxide semiconductor field-effect transistor (MOSFET) detector, the response of the detector depends strongly on the linear energy transfer. The present study reports a practical method to correct the MOSFET response for linear energy transfer dependence by using a simplified Monte Carlo dose calculation method (SMC). A depth-output curve for a mono-energetic proton beam in polyethylene was measured with the MOSFET detector. This curve was used to calculate MOSFET output distributions with the SMC (SMC(MOSFET)). The SMC(MOSFET) output value at an arbitrary point was compared with the value obtained by the conventional SMC(PPIC), which calculates proton dose distributions by using the depth-dose curve determined by a parallel-plate ionization chamber (PPIC). The ratio of the two values was used to calculate the correction factor of the MOSFET response at an arbitrary point. The dose obtained by the MOSFET detector was determined from the product of the correction factor and the MOSFET raw dose. When in vivo proton dosimetry was performed with the MOSFET detector in an anthropomorphic phantom, the corrected MOSFET doses agreed with the SMC(PPIC) results within the measurement error. To our knowledge, this is the first report of successful in vivo proton dosimetry with a MOSFET detector.

Gabapentin treatment for alcohol dependence: a randomized clinical trial.

PubMed

Mason, Barbara J; Quello, Susan; Goodell, Vivian; Shadan, Farhad; Kyle, Mark; Begovic, Adnan

2014-01-01

Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics. To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner. A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital. Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling. Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups. Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence. clinicaltrials.gov Identifier: NCT00391716.

Characteristics of an OSLD in the diagnostic energy range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Senan, Rani M.; Hatab, Mustapha R.

2011-07-15

Purpose: Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. Methods: NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energymore » dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Results: Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R{sup 2} > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 deg. in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). Conclusions: OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.« less

Radiation-chemical and optical properties of a radio-fluorogenic gel

NASA Astrophysics Data System (ADS)

Yao, Tiantian; Gasparini, Alessia; Denkova, Antonia G.; Warman, John M.

2015-01-01

The radiation-induced polymerization and fluorescence intensity of a radio- fluorogenic medium consisting of tertiary-butyl acrylate (TBA) with ca 100 ppm maleimido- pyrene (MPy) display a super-linear dependence on dose and a close to inverse square root dependence on dose rate over the range from 2 to 30 Gy/min. In contrast with the fluorescence, the clarity and optical absorption remain unchanged on irradiation up to at least 17% monomer conversion for which the medium is a rigid gel.

Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Poston, J. W.; Cucinotta, F. A.; Wilson, J. W.

1996-01-01

During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Y; Scott, A; Allahverdian, J

2014-06-15

Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80,more » 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT.« less

Nonclinical pharmacokinetic and pharmacodynamic characterisation of somapacitan: A reversible non-covalent albumin-binding growth hormone.

PubMed

Thygesen, Peter; Andersen, Henrik Sune; Behrens, Carsten; Fels, Johannes Josef; Nørskov-Lauritsen, Leif; Rischel, Christian; Johansen, Nils Langeland

2017-08-01

Somapacitan is an albumin-binding growth hormone derivative intended for once weekly administration, currently in clinical development for treatment of adult as well as juvenile GH deficiency. Nonclinical in vivo pharmacological characterisation of somapacitan was performed to support the clinical trials. Here we present the pharmacokinetic and pharmacodynamic effects of somapacitan in rats, minipigs, and cynomolgus monkeys. Pharmacokinetic studies investigating exposure, absorption, clearance, and bioavailability after single intravenous (i.v.) and subcutaneous (s.c.) administration were performed in all species. A dose-response study with five dose levels and a multiple dose pharmacodynamic study with four once weekly doses was performed in hypophysectomised rats to evaluate the effect of somapacitan on growth and IGF-I production. Pharmacokinetic profiles indicated first order absorption from the subcutaneous tissue after s.c. injections for somapacitan in all three species. Apparent terminal half-lives were 5-6h in rats, 10-12h in minipigs, and 17-20h in monkeys. Somapacitan induced a dose-dependent growth in hypophysectomised rats (p<0.001) and an increase in plasma IGF-I levels in rats (p<0.01), minipigs (p<0.01), and cynomolgus monkeys (p<0.05) after single dose administration. Multiple once weekly dosing of somapacitan in hypophysectomised rats induced a step-wise increase in body weight with an initial linear phase the first 3-4days in each dosing interval (p<0.001). The nonclinical pharmacokinetic and pharmacodynamic studies of somapacitan showed similar pharmacokinetic properties, with no absorption-limited elimination, increased clearance and increased and sustained levels of IGF-I in plasma for up to 10days after a single dose administration in all three species. Somapacitan induced a dose-dependent increase in body weight and IGF-I levels in hypophysectomised rats. Multiple dosing of somapacitan in hypophysectomised rats suggested a linear growth for the first 3-4days in each weekly dosing interval, whereas daily hGH dosing showed linear growth for approximately two weeks before reaching a plateau level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose-dependent misrejoining of radiation-induced DNA double-strand breaks in human fibroblasts: Experimental and theoretical study for high and low LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rydberg, Bjorn; Cooper, Brian; Cooper, Priscilla K.

2004-11-18

Misrejoining of DNA double-strand breaks (DSBs) was measured in human primary fibroblasts after exposure to X-rays and high LET particles (He, N and Fe) in the dose range 10-80 Gy. To measure joining of wrong DNA ends, the integrity of a 3.2 Mbp restriction fragment was analyzed directly after exposure and after 16 hr of repair incubation. It was found that the misrejoining frequency for X-rays was non-linearly related to dose, with less probability of misrejoining at low doses than at high doses. The dose dependence for the high LET particles, on the other hand, was closer to being linear,more » with misrejoining frequencies higher than for X-rays particularly at the lower doses. These experimental results were simulated with a Monte-Carlo approach that includes a cell nucleus model with all 46 chromosomes present, combined with realistic track structure simulations to calculate the geometrical positions of all DSBs induced for each dose. The model assumes that the main determinant for misrejoining probability is the distance between two simultaneously present DSBs. With a Gaussian interaction probability function with distance, it was found that both the low and high LET data could be fitted with an interaction distance (sigma of the Gaussian curve) of 0.25 {micro}m. This is half the distance previously found to best fit chromosomal aberration data in human lymphocytes using the same methods (Holley et al. Radiat. Res . 158, 568-580 (2002)). The discrepancy may indicate inadequacies in the chromosome model, for example insufficient chromosomal overlap, but may also partly be due to differences between fibroblasts and lymphocytes. Although the experimental data was obtained at high doses, the Monte Carlo calculations could be extended to lower doses. It was found that a linear component of misrejoining versus dose dominated for doses below 1 Gy for all radiations, including X-rays. The calculated relative biological efficiency (RBE) for misrejoining at this low dose region was 31 for the He-ions, 28 for the N-ions and 19 for Fe-ions.« less

Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safari, M. J.; Wong, J. H. D.; Ng, K. H., E-mail: ngkh@um.edu.my

2015-05-15

Purpose: The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. Methods: The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualitiesmore » were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. Results: The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (±1%), field size (±1%), frame rate (±3%), or beam energy (±5%). The detector angular dependence was within ±5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ±3%. Conclusions: The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.« less

Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures.

PubMed

Safari, M J; Wong, J H D; Ng, K H; Jong, W L; Cutajar, D L; Rosenfeld, A B

2015-05-01

The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualities were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (± 1%), field size (± 1%), frame rate (± 3%), or beam energy (± 5%). The detector angular dependence was within ± 5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ± 3%. The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.

Characterization of a new transmission detector for patient individualized online plan verification and its influence on 6MV X-ray beam characteristics.

PubMed

Thoelking, Johannes; Sekar, Yuvaraj; Fleckenstein, Jens; Lohr, Frank; Wenz, Frederik; Wertz, Hansjoerg

2016-09-01

Online verification and 3D dose reconstruction on daily patient anatomy have the potential to improve treatment delivery, accuracy and safety. One possible implementation is to recalculate dose based on online fluence measurements with a transmission detector (TD) attached to the linac. This study provides a detailed analysis of the influence of a new TD on treatment beam characteristics. The influence of the new TD on surface dose was evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build-up region. Based on Monte Carlo simulations, correction factors were determined to scale down the over-response of the Adv-MC close to the surface. To analyze the effects beyond dmax percentage depth dose (PDD), lateral profiles and transmission measurements were performed. All measurements were carried out for various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck, prostate, thorax) and 2 manually created test cases (3×3cm(2) fields with different dose levels, sweeping gap) were measured to investigate the influence of the TD on clinical treatment plans. To investigate the performance of the TD, dose linearity as well as dose rate dependency measurements were performed. With the TD inside the beam an increase in surface dose was observed depending on SSD and field size (maximum of +11%, SSD = 80cm, field size = 30×30cm(2)). Beyond dmax the influence of the TD on PDDs was below 1%. The measurements showed that the transmission factor depends slightly on the field size (0.893-0.921 for 5×5cm(2) to 30×30cm(2)). However, the evaluation of clinical IMRT-plans measured with and without the TD showed good agreement after using a single transmission factor (γ(2%/2mm) > 97%, δ±3% >95%). Furthermore, the response of TD was found to be linear and dose rate independent (maximum difference <0.5% compared to reference measurements). When placed in the path of the beam, the TD introduced a slight, clinically acceptable increase of the skin dose even for larger field sizes and smaller SSDs and the influence of the detector on the dose beyond dmax as well as on clinical IMRT-plans was negligible. Since there was no dose rate dependency and the response was linear, the device is therefore suitable for clinical use. Only its absorption has to be compensated during treatment planning, either by the use of a single transmission factor or by including the TD in the incident beam model. Copyright © 2015. Published by Elsevier GmbH.

Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance.

PubMed

Pardo, J; Franco, L; Gómez, F; Iglesias, A; Pazos, A; Pena, J; Lobato, R; Mosquera, J; Pombar, M; Sendón, J

2005-04-21

A liquid isooctane (C(8)H(18)) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm x 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles such as those present in intensity modulated radiation therapy (IMRT) and radiosurgery. As the read-out electronics we use the X-ray Data Acquisition System with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests, we have studied dose rate and energy dependences. Dose rate dependence was found to be lower than 2.1% up to 5 Gy min(-1), and energy dependence lower than 2.5% up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm(3) air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal-to-noise ratio.

SU-E-T-526: On the Linearity, Stability and Beam Energy Dependence of CdSe Quantum Dots as Scintillating Probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delage, M-E; Centre Hospitalier Universityde Quebec, Quebec, QC; Lecavalier, M-E

2014-06-01

Purpose: Structure and energy transfer mechanisms confer colloidal quantum dots (cQDs) interesting properties, among them their potential as scintillators. CdSe multi-shell cQDs in powder were investigated under photons irradiation. The purpose of this work is to characterize signal to dose linearity, stability with time and to quantify the dependence of their light output with beam energy. Methods: The cQDs are placed at the extremity of a non-scintillating plastic collecting fiber, with the other extremity connected to an Apogee U2000C CCD camera. The CCD camera collects the fluorescence light from irradiated cQDs from which the delivered dose is extracted. This signalmore » is corrected for Cerenkov contamination at MV energies using the chromatic technique. The detector was irradiated with two devices: Xstrahl 200 orthovoltage unit for 120, 180 and 220 kVp and a Varian Clinac iX for 6 and 23 MV. Results: Linear output response with varying dose is observed for all beam energies with R2 factors > 0,999. Reproducibility measurements were performed at 120 kVp: the same set-up was irradiated at different time intervals (one week and three months). The results showed only a small relative decrease of light output of 3,2 % after a combine deposited dose of approximately 95 Gy. CdSe nanocrystals response has been studied as a function of beam energy. The output increases with decreasing energy from 120 kVp to 6 MV and increase again for 23 MV. This behavior could be explained in part by the cQDs high-Z composition. Conclusion: The fluorescence light output of CdSe cQDs was found to be linear as a function of dose. The results suggest stability of the scintillation output of cQDs over time. The specific composition of cQDs is the main cause of the observed energy dependence. We will further look into particle beam dependence of the cQDs. Bourse d'excellence aux etudes graduees du CRC (Centre de Recherche sur le Cancer, Universite Laval) Bourse d'excellence aux etudes graduees du CRC (Centre de Recherche sur le Cancer, Universite Laval)« less

The modified unified interaction model: incorporation of dose-dependent localised recombination.

PubMed

Lavon, A; Eliyahu, I; Oster, L; Horowitz, Y S

2015-02-01

The unified interaction model (UNIM) was developed to simulate thermoluminescence (TL) linear/supralinear dose-response and the dependence of the supralinearity on ionisation density, i.e. particle type and energy. Before the development of the UNIM, this behaviour had eluded all types of TL modelling including conduction band/valence band (CB/VB) kinetic models. The dependence of the supralinearity on photon energy was explained in the UNIM as due to the increasing role of geminate (localised recombination) with decreasing photon/electron energy. Recently, the Ben Gurion University group has incorporated the concept of trapping centre/luminescent centre (TC/LC) spatially correlated complexes and localised/delocalised recombination into the CB/VB kinetic modelling of the LiF:Mg,Ti system. Track structure considerations are used to describe the relative population of the TC/LC complexes by an electron-hole or by an electron-only as a function of both photon/electron energy and dose. The latter dependence was not included in the original UNIM formulation, a significant over-simplification that is herein corrected. The modified version, the M-UNIM, is then applied to the simulation of the linear/supralinear dose-response characteristics of composite peak 5 in the TL glow curve of LiF:Mg,Ti at two representative average photon/electron energies of 500 and 8 keV. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reproducibility of CVD diamond detectors for radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Betzel, G. T.; Lansley, S. P.; McKay, D.; Meyer, J.

2012-11-01

Three in-house X-ray detectors based on diamond chemical vapor deposition (CVD) from the same manufactured batch of single crystal films were investigated for their reproducibility. Leakage current, priming dose, response dynamics, dose linearity, dependence on dose rate and angular dependence were used to evaluate differences between detectors. Slight differences were seen in leakage currents before (<1.5 pA) and after (<12 pA) irradiation. A priming dose of ˜7 Gy and rise and fall times of 2 s were found for all three detectors. Sensitivities differed by up to 10%. Dependence on dose rate were similar (∆=0.92-0.94). Angular dependence was minimal (97-102% avg.). Differences in detector performance appeared to be primarily due to film thickness, which can significantly change sensitivities (nC Gy-1) and applied fields (V μm-1) for detectors with small sensitive volumes. Results suggest that preselection of CVD diamond films according to thickness in addition to material quality would be required to avoid individual calibration, which is performed for commercially available natural diamond detectors.

A reusable OSL-film for 2D radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-11-01

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film’s reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after ‘beam on’ or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min-1) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film’s measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

A reusable OSL-film for 2D radiotherapy dosimetry.

PubMed

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-10-19

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff ). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film's reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after 'beam on' or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min -1 ) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film's measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

Variation of rabbit sperm physiologic parameters after the X-ray exposure.

PubMed

Klepko, A V; Gorban, L V; Motryna, O A; Kondratova, Y A; Chernyshov, A V; Andreychenko, S V

2013-01-01

To study the impact of X-irradiation on the morpho-functional characteristics of rabbit spermatozoa and the contents of fructose, L-carnitine, α-tocopherol, ascorbate and citrate in the animal sperm. The total body irradiation of rabbits (Soviet Shinchilla) was performed at the RUM-17 device in the dose range of 1.0-7.0 Gy with 2.8·10-3 Gy/sec intensity. The animal sperm was collected by the artificial vagina and then separated on seminal plasma and spermatozoa through centrifugation. Sperm concentration, motility, morphology and linear velocity were identified using the "MBI-6" light microscope. The quantitative determination of ascorbate, α-tocopherol and L-carnitine in seminal plasma was made on the "Agilent 1200" liquid chromatograph, while the concentration of fructose and citrate was measured on a spectrophotometer. The X-ray irradiation was shown to cause a dose-dependent suppressing effect on the prostate, seminal vesicles and epididymices expresed through the decreased content of fructose, citrate, L-carnitine, α-tocopherol and ascorbate in a rabbit sperm. Simultaneously the exacerbation of morphologic anomalies (damage of acrosomes, heads and tails) in spermatozoa along with spermatozoid motility and linear velocity decrease were elucidated. The run-time pattern of morpho-functional changes in spermatozoa together with component content of rabbit sperm in response to the total body irradiation was studied. Consequently the dose dependent raise of morphologic anomalies (damage of acrosomes, heads and tails) in spermatozoa and the slowing of spermatozoid linear velocity was found out. The sperm capacity to fulfill the post-radiation recovery was proven up. The effectiveness of the latter was shown to be dependent upon the radiation dose absorbed and the duration of post-irradiation period. Klepko A. V., Gorban L. V., Motryna O. A., Kondratova Ju. A., Chernyshov A. V., Andrejchenko S. V., 2013.

Organometallic exposure dependence on organic–inorganic hybrid material formation in polyethylene terephthalate and polyamide 6 polymer fibers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akyildiz, Halil I.; Jur, Jesse S., E-mail: jsjur@ncsu.edu

2015-03-15

The effect of exposure conditions and surface area on hybrid material formation during sequential vapor infiltrations of trimethylaluminum (TMA) into polyamide 6 (PA6) and polyethylene terephthalate (PET) fibers is investigated. Mass gain of the fabric samples after infiltration was examined to elucidate the reaction extent with increasing number of sequential TMA single exposures, defined as the times for a TMA dose and a hold period. An interdependent relationship between dosing time and holding time on the hybrid material formation is observed for TMA exposure PET, exhibited as a linear trend between the mass gain and total exposure (dose time ×more » hold time × number of sequential exposures). Deviation from this linear relationship is only observed under very long dose or hold times. In comparison, amount of hybrid material formed during sequential exposures to PA6 fibers is found to be highly dependent on amount of TMA dosed. Increasing the surface area of the fiber by altering its cross-sectional dimension is shown to have little on the reaction behavior but does allow for improved diffusion of the TMA into the fiber. This work allows for the projection of exposure parameters necessary for future high-throughput hybrid modifications to polymer materials.« less

In vivo proton dosimetry using a MOSFET detector in an anthropomorphic phantom with tissue inhomogeneity

PubMed Central

Hotta, Kenji; Matsubara, Kana; Nishioka, Shie; Matsuura, Taeko; Kawashima, Mitsuhiko

2012-01-01

When in vivo proton dosimetry is performed with a metal‐oxide semiconductor field‐effect transistor (MOSFET) detector, the response of the detector depends strongly on the linear energy transfer. The present study reports a practical method to correct the MOSFET response for linear energy transfer dependence by using a simplified Monte Carlo dose calculation method (SMC). A depth‐output curve for a mono‐energetic proton beam in polyethylene was measured with the MOSFET detector. This curve was used to calculate MOSFET output distributions with the SMC (SMCMOSFET). The SMCMOSFET output value at an arbitrary point was compared with the value obtained by the conventional SMCPPIC, which calculates proton dose distributions by using the depth‐dose curve determined by a parallel‐plate ionization chamber (PPIC). The ratio of the two values was used to calculate the correction factor of the MOSFET response at an arbitrary point. The dose obtained by the MOSFET detector was determined from the product of the correction factor and the MOSFET raw dose. When in vivo proton dosimetry was performed with the MOSFET detector in an anthropomorphic phantom, the corrected MOSFET doses agreed with the SMCPPIC results within the measurement error. To our knowledge, this is the first report of successful in vivo proton dosimetry with a MOSFET detector. PACS number: 87.56.‐v PMID:22402385

A new method for calculation of the chlorine demand of natural and treated waters.

PubMed

Warton, Ben; Heitz, Anna; Joll, Cynthia; Kagi, Robert

2006-08-01

Conventional methods of calculating chlorine demand are dose dependent, making intercomparison of samples difficult, especially in cases where the samples contain substantially different concentrations of dissolved organic carbon (DOC), or other chlorine-consuming species. Using the method presented here, the values obtained for chlorine demand are normalised, allowing valid comparison of chlorine demand between samples, independent of the chlorine dose. Since the method is not dose dependent, samples with substantially differing water quality characteristics can be reliably compared. In our method, we dosed separate aliquots of a water sample with different chlorine concentrations, and periodically measured the residual chlorine concentrations in these subsamples. The chlorine decay data obtained in this way were then fitted to first-order exponential decay functions, corresponding to short-term demand (0-4h) and long-term demand (4-168 h). From the derived decay functions, the residual concentrations at a given time within the experimental time window were calculated and plotted against the corresponding initial chlorine concentrations, giving a linear relationship. From this linear function, it was then possible to determine the residual chlorine concentration for any initial concentration (i.e. dose). Thus, using this method, the initial chlorine dose required to give any residual chlorine concentration can be calculated for any time within the experimental time window, from a single set of experimental data.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

In vivo dose response relationship between physostigmine and cholinesterase activity in RBC and tissues of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somani, S.M.; Dube, S.N.

1989-01-01

Dose response of physostigmine (Phy) was studied in rat using various doses. Rats were sacrificed 15 min after Phy administration. Blood and tissues were analyzed for ChE activity by radiometric method and Phy concentration by HPLC method. A comparison of ChE values in different tissues of rats indicated that ChE activity was highest in brain and least in diaphragm. The enzyme activity was eleven times more in brain as compared to diaphragm. Phy produced a dose-dependent inhibition of ChE in RBC, brain and diaphragm from 50 to 200 {mu}g/kg, then ChE inhibition was plateaued from 200 to 500 {mu}g/kg inmore » these tissues. A dose related ChE inhibition was seen in heart and thigh muscle from 50 to 500 {mu}g/kg. Phy concentration increased linearly from 50 to 400 {mu}g/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 {mu}g/kg in RBC, 150 {mu}g/kg in brain and 300 {mu}g/kg in heart. This linearity is not consistent in other tissues.« less

INTERCOMPARISON ON THE MEASUREMENT OF THE QUANTITY PERSONAL DOSE EQUIVALENT HP(10) IN PHOTON FIELDS. LINEARITY DEPENDENCE, LOWER LIMIT OF DETECTION AND UNCERTAINTY IN MEASUREMENT OF DOSIMETRY SYSTEMS OF INDIVIDUAL MONITORING SERVICES IN GABON AND GHANA.

PubMed

Ondo Meye, P; Schandorf, C; Amoako, J K; Manteaw, P O; Amoatey, E A; Adjei, D N

2017-12-01

An inter-comparison study was conducted to assess the capability of dosimetry systems of individual monitoring services (IMSs) in Gabon and Ghana to measure personal dose equivalent Hp(10) in photon fields. The performance indicators assessed were the lower limit of detection, linearity and uncertainty in measurement. Monthly and quarterly recording levels were proposed with corresponding values of 0.08 and 0.025 mSv, and 0.05 and 0.15 mSv for the TLD and OSL systems, respectively. The linearity dependence of the dosimetry systems was performed following the requirement given in the Standard IEC 62387 of the International Electrotechnical Commission (IEC). The results obtained for the two systems were satisfactory. The procedure followed for the uncertainty assessment is the one given in the IEC technical report TR62461. The maximum relative overall uncertainties, in absolute value, expressed in terms of Hp(10), for the TL dosimetry system Harshaw 6600, are 44. 35% for true doses below 0.40 mSv and 36.33% for true doses ≥0.40 mSv. For the OSL dosimetry system microStar, the maximum relative overall uncertainties, in absolute value, are 52.17% for true doses below 0.40 mSv and 37.43% for true doses ≥0.40 mSv. These results are in good agreement with the requirements for accuracy of the International Commission on Radiological protection. When expressing the uncertainties in terms of response, comparison with the IAEA requirements for overall accuracy showed that the uncertainty results were also acceptable. The values of Hp(10) directly measured by the two dosimetry systems showed a significant underestimation for the Harshaw 6600 system, and a slight overestimation for the microStar system. After correction for linearity of the measured doses, the two dosimetry systems gave better and comparable results. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Performance traits and metabolic responses in goats (Capra hircus) supplemented with inorganic trivalent chromium.

PubMed

Haldar, Sudipto; Mondal, Souvik; Samanta, Saikat; Ghosh, Tapan Kumar

2009-11-01

The effects of supplemental chromium (Cr) as chromic chloride hexahydrate in incremental dose levels (0, 0.5, 1.0, and 1.5 mg/day for 240 days) on metabolism of nutrients and trace elements were determined in dwarf Bengal goats (Capra hircus, castrated males, average age 3 months, n = 24, initial mean body weight 6.4 +/- 0.22 kg). Live weight increased linearly (p < 0.05) with the level of supplemental Cr. Organic matter and crude protein digestibility, intake of total digestible nutrients, and retention of N (g/g N intake) increased (p < 0.05) in a dose-dependent linear manner. Serum cholesterol and tryacylglycerol concentrations changed inversely with the dose of supplemental Cr (p < 0.01). Supplemental Cr positively influenced retention of copper and iron (p < 0.05) causing linear increase (p < 0.01) in their serum concentrations. It was concluded that Cr supplementation may improve utilization of nutrients including the trace elements and may also elicit a hypolidemic effect in goats. However, further study with regards to optimization of dose is warranted.

Characterization of the Exradin W1 scintillator for use in radiotherapy.

PubMed

Carrasco, P; Jornet, N; Jordi, O; Lizondo, M; Latorre-Musoll, A; Eudaldo, T; Ruiz, A; Ribas, M

2015-01-01

To evaluate the main characteristics of the Exradin W1 scintillator as a dosimeter and to estimate measurement uncertainties when used in radiotherapy. We studied the calibration procedure, energy and modality dependence, short-term repeatability, dose-response linearity, angular dependence, temperature dependence, time to reach thermal equilibrium, dose-rate dependence, water-equivalent depth of the effective measurement point, and long-term stability. An uncertainty budget was derived for relative and absolute dose measurements in photon and electron beams. Exradin W1 showed a temperature dependence of -0.225% °C(-1). The loss of sensitivity with accumulated dose decreased with use. The sensitivity of Exradin W1 was energy independent for high-energy photon and electron beams. All remaining dependencies of Exradin W1 were around or below 0.5%, leading to an uncertainty budget of about 1%. When a dual channel electrometer with automatic trigger was not used, timing effects became significant, increasing uncertainties by one order of magnitude. The Exradin W1 response is energy independent for high energy x-rays and electron beams, and only one calibration coefficient is needed. A temperature correction factor should be applied to keep uncertainties around 2% for absolute dose measurements and around 1% for relative measurements in high-energy photon and electron beams. The Exradin W1 scintillator is an excellent alternative to detectors such as diodes for relative dose measurements.

Biological X-ray irradiator characterization for use with small animals and cells.

PubMed

Bruno, A Colello; Mazaro, S J; Amaral, L L; Rego, E M; Oliveira, H F; Pavoni, J F

2017-03-02

This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current), the radiometric survey (leakage radiation) and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1) and remained stable for long (constant) and short (repeatability) intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer). The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators) for cells and small animal irradiation, especially in early research stages.

Characterization of optically stimulated luminescent dosimeters, OSLDs, for clinical dosimetric measurements.

PubMed

Jursinic, Paul A

2007-12-01

Optically stimulated luminescent dosimeters, OSLDs, are plastic disks infused with aluminum oxide doped with carbon (Al2O3 : C). These disks are encased in a light-tight plastic holder. Crystals of Al2O3 : C when exposed to ionizing radiation store energy that is released as luminescence (420 nm) when the OSLD is illuminated with stimulation light (540 nm). The intensity of the luminescence depends on the dose absorbed by the OSLD and the intensity of the stimulation light. OSLDs used in this work were InLight/OSL Dot dosimeters, which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). The following are dosimetric properties of the OSLD that were determined: After a single irradiation, repeated readings cause the signal to decrease by 0.05% per reading; the signal could be discharged by greater than 98% by illuminating them for more than 45 s with a 150 W tungsten-halogen light; after irradiation there was a transient signal that decayed with a 0.8 min halftime; after the transient signal decay the signal was stable for days; repeated irradiations and readings of an individual OSLD gave a signal with a coefficient of variation of 0.6%; the dose sensitivity of OSLDs from a batch of detectors has a coefficient of variation of 0.9%, response was linear with absorbed dose over a test range of 1-300 cGy; above 300 cGy a small supra-linear behavior occurs; there was no dose-per-pulse dependence over a 388-fold range; there was no dependence on radiation energy or mode for 6 and 15 MV x rays and 6-20 MeV electrons; for Ir-192 gamma rays OSLD had 6% higher sensitivity; the dose sensitivity was unchanged up to an accumulated dose of 20 Gy and thereafter decreased by 4% per 10 Gy of additional accumulated dose; dose sensitivity was not dependent on the angle of incidence of radiation; the OSLD in its light-tight case has an intrinsic buildup of 0.04 g/cm2; dose sensitivity of the OSLD was not dependent on temperature at the time of irradiation in the range of 10-40 degrees C. The clinical use of OSLDs for in vivo dosimetric measurements is shown to be feasible.

Characterization of optically stimulated luminescent dosimeters, OSLDs, for clinical dosimetric measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jursinic, Paul A.

2007-12-15

Optically stimulated luminescent dosimeters, OSLDs, are plastic disks infused with aluminum oxide doped with carbon (Al{sub 2}O{sub 3}:C). These disks are encased in a light-tight plastic holder. Crystals of Al{sub 2}O{sub 3}:C when exposed to ionizing radiation store energy that is released as luminescence (420 nm) when the OSLD is illuminated with stimulation light (540 nm). The intensity of the luminescence depends on the dose absorbed by the OSLD and the intensity of the stimulation light. OSLDs used in this work were InLight/OSL Dot dosimeters, which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). The following are dosimetricmore » properties of the OSLD that were determined: After a single irradiation, repeated readings cause the signal to decrease by 0.05% per reading; the signal could be discharged by greater than 98% by illuminating them for more than 45 s with a 150 W tungsten-halogen light; after irradiation there was a transient signal that decayed with a 0.8 min halftime; after the transient signal decay the signal was stable for days; repeated irradiations and readings of an individual OSLD gave a signal with a coefficient of variation of 0.6%; the dose sensitivity of OSLDs from a batch of detectors has a coefficient of variation of 0.9%, response was linear with absorbed dose over a test range of 1-300 cGy; above 300 cGy a small supra-linear behavior occurs; there was no dose-per-pulse dependence over a 388-fold range; there was no dependence on radiation energy or mode for 6 and 15 MV x rays and 6-20 MeV electrons; for Ir-192 gamma rays OSLD had 6% higher sensitivity; the dose sensitivity was unchanged up to an accumulated dose of 20 Gy and thereafter decreased by 4% per 10 Gy of additional accumulated dose; dose sensitivity was not dependent on the angle of incidence of radiation; the OSLD in its light-tight case has an intrinsic buildup of 0.04 g/cm{sup 2}; dose sensitivity of the OSLD was not dependent on temperature at the time of irradiation in the range of 10-40 deg. C. The clinical use of OSLDs for in vivo dosimetric measurements is shown to be feasible.« less

[Evaluation of an Experimental Production Wireless Dose Monitoring System for Radiation Exposure Management of Medical Staff].

PubMed

Fujibuchi, Toshioh; Murazaki, Hiroo; Kuramoto, Taku; Umedzu, Yoshiyuki; Ishigaki, Yung

2015-08-01

Because of the more advanced and more complex procedures in interventional radiology, longer treatment times have become necessary. Therefore, it is important to determine the exposure doses received by operators and patients. The aim of our study was to evaluate an experimental production wireless dose monitoring system for pulse radiation in diagnostic X-ray. The energy, dose rate, and pulse fluoroscopy dependence were evaluated as the basic characteristics of this system for diagnostic X-ray using a fully digital fluoroscopy system. The error of 1 cm dose equivalent rate was less than 15% from 35.1 keV to 43.2 keV with energy correction using metal filter. It was possible to accurately measure the dose rate dependence of this system, which was highly linear until 100 μSv/h. This system showed a constant response to the pulse fluoroscopy. This system will become useful wireless dosimeter for the individual exposure management by improving the high dose rate and the energy characteristics.

Effects of a Multi-Ingredient Energy Supplement on Cognitive Performance and Cerebral-Cortical Activation.

PubMed

Daou, Marcos; Sassi, Julia Montagner; Miller, Matthew W; Gonzalez, Adam M

2018-03-13

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η 2 p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η 2 p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

TLD linearity vs. beam energy and modality.

PubMed

Troncalli, Andrew J; Chapman, Jane

2002-01-01

Thermoluminescent dosimetry (TLD) is considered to be a valuable dosimetric tool in determining patient dose. Lithium fluoride doped with magnesium and titanium (TLD-100) is widely used, as it does not display widely divergent energy dependence. For many years, we have known that TLD-100 shows supralinearity to dose. In a radiotherapy clinic, there are multiple energies and modality beams. This work investigates whether individual linearity corrections must be used for each beam or whether a single correction can be applied to all beams. The response of TLD as a function of dose was measured from 25 cGy to 1000 cGy on both electrons and photons from 6 to 18 MeV. This work shows that, within our measurement uncertainty, TLD-100 exhibits supralinearity at all megavoltage energies and modalities.

General radiographic attributes of optically stimulated luminescence dosimeters: A basic insight

NASA Astrophysics Data System (ADS)

Musa, Y.; Hashim, S.; Ghoshal, S. K.; Bradley, D. A.; Ahmad, N. E.; Karim, M. K. A.; Hashim, A.; Kadir, A. B. A.

2018-06-01

We report the ubiquitous radiographic characteristics of optically stimulated luminescence dosimeters (OSLD) so called nanoDot OSLDs (Landauer Inc., Glendwood, IL). The X-ray irradiations were performed in free air ambiance to inspect the repeatability, the reproducibility, the signal depletion, the element correction factors (ECFs), the dose response and the energy dependence. Repeatability of multiple readouts after single irradiation to 10 mGy revealed a coefficient of variation below 3%, while the reproducibility in repeated irradiation-readout-annealing cycles was above 2%. The OSL signal depletion for three nanoDots with simultaneous irradiation to 20 mGy and sequential readouts of 25 times displayed a consistent signal reduction ≈0.5% per readout with R2 values over 0.98. ECFs for individual OSLDs were varied from 0.97 to 1.03. In the entire dose range under 80 kV, a good linearity with an R2 exceeding 0.99 was achieved. Besides, the percentage difference between OSLD and ion-chamber dose was less than 5%, which was superior to TLD. The X-ray photon irradiated energy response factors (between 0.76 and 1.12) in the range of 40-150 kV (26.1-61.2 keV) exhibited significant energy dependence. Indeed, the nanoDot OSLDs disclosed good repeatability, reproducibility and linearity. The OSLDs measured doses were closer to ion-chamber doses than that of TLD. It can be further improved up to ≈3% by applying the individual dosimeter ECF. On top, the energy dependent uncertainties can be minimized using the energy correction factors. It is established that the studied nanoDot OSLDs are prospective for measuring entrance dose in general radiographic practices.

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring.

PubMed

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min -1 . Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean : R 2   =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring

NASA Astrophysics Data System (ADS)

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min-1. Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean: R 2  =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.

PubMed

Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

2013-09-01

Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

Dosimetric characteristics of a PIN diode for radiotherapy application.

PubMed

Kumar, R; Sharma, S D; Philomina, A; Topkar, A

2014-08-01

The PIN diode developed by Bhabha Atomic Research Centre (BARC) was modified for its use as a dosimeter in radiation therapy. For this purpose the diode was mounted on a printed circuit board (PCB) and provided with necessary connections so that its response against irradiation can be recorded by a standard radiotherapy electrometer. The dosimetric characteristics of the diode were studied in Co-60 gamma rays as well as high energy X-rays. The measured sensitivity of this PIN diode is 4 nC/cGy which is about ten times higher than some commercial diode dosimeters. The leakage current from the diode is 0.04 nA. The response of the PIN diode is linear in the range of 20-1000 cGy which covers the full range of radiation dose encountered in radiotherapy treatments. The non-linearity of the diode response is 3.5% at 20 cGy and it is less than 1.5% at higher dose values. Its repeatability is within 0.5%. The angular response variation is about 5.6% within 6608 with respect to normal beam incidence. The response of the PIN diode at 6 and 18 MV X-rays varies within 2% with respect to its response at Co-60 gamma rays. The source to surface distance (SSD) dependence of the PIN diode was studied for Co-60 beam. It was found that the response of the diode decreases almost linearly relative to given dose for beams with constant collimator setting but increasing SSD (decreasing dose-rate). Within this study the diode response varied by about 2.5% between the maximum and minimum SSD. The dose-rate dependence of the PIN diode for 6 and 15 MV-rays was studied. The variation in response of diode for both energies in the studied dose range is less than 1%. The field size dependence of the PIN diode response is within 1% with respect to the response of ionisation chamber. These studies indicate that the characteristics of the PIN diode are suitable for use in radiotherapy dosimetry.

Dose dependence of true stress parameters in irradiated bcc, fcc, and hcp metals

NASA Astrophysics Data System (ADS)

Byun, T. S.

2007-04-01

The dose dependence of true stress parameters has been investigated for nuclear structural materials: A533B pressure vessel steels, modified 9Cr-1Mo and 9Cr-2WVTa ferritic martensitic steels, 316 and 316LN stainless steels, and Zircaloy-4. After irradiation to significant doses, these alloys show radiation-induced strengthening and often experience prompt necking at yield followed by large necking deformation. In the present work, the critical true stresses for deformation and fracture events, such as yield stress (YS), plastic instability stress (PIS), and true fracture stress (FS), were obtained from uniaxial tensile tests or calculated using a linear strain-hardening model for necking deformation. At low dose levels where no significant embrittlement was detected, the true fracture stress was nearly independent of dose. The plastic instability stress was also independent of dose before the critical dose-to-prompt-necking at yield was reached. A few bcc alloys such as ferritic martensitic steels experienced significant embrittlement at doses above ∼1 dpa; and the true fracture stress decreased with dose. The materials fractured before yield at or above 10 dpa.

Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. III. Dose-response pattern of mutation induction in UV-irradiated rev2ts cells.

PubMed

Siede, W; Eckardt, F

1986-01-01

Recent studies regarding the influence of cycloheximide on the temperature-dependent increase in survival and mutation frequencies of a thermoconditional rev2 mutant lead to the suggestion that the REV2-coded mutagenic repair function is UV-inducible. In the present study we show that stationary-phase rev2ts cells are characterized by a biphasic linear-quadratic dose-dependence of mutation induction ("mutation kinetics") of ochre alleles at 23 degrees C (permissive temperature) but linear kinetics at the restrictive temperature of 36 degrees C. Mathematical analysis using a model based on Poisson statistics and a further mathematical procedure, the calculation of "apparent survival", support the assumption that the quadratic component of the reverse mutation kinetics investigated can be attributed to a UV-inducible component of mutagenic DNA repair controlled by the REV2 gene.

The role of a microDiamond detector in the dosimetry of proton pencil beams.

PubMed

Gomà, Carles; Marinelli, Marco; Safai, Sairos; Verona-Rinati, Gianluca; Würfel, Jan

2016-03-01

In this work, the performance of a microDiamond detector in a scanned proton beam is studied and its potential role in the dosimetric characterization of proton pencil beams is assessed. The linearity of the detector response with the absorbed dose and the dependence on the dose-rate were tested. The depth-dose curve and the lateral dose profiles of a proton pencil beam were measured and compared to reference data. The feasibility of calibrating the beam monitor chamber with a microDiamond detector was also studied. It was found the detector reading is linear with the absorbed dose to water (down to few cGy) and the detector response is independent of both the dose-rate (up to few Gy/s) and the proton beam energy (within the whole clinically-relevant energy range). The detector showed a good performance in depth-dose curve and lateral dose profile measurements; and it might even be used to calibrate the beam monitor chambers-provided it is cross-calibrated against a reference ionization chamber. In conclusion, the microDiamond detector was proved capable of performing an accurate dosimetric characterization of proton pencil beams. Copyright © 2015. Published by Elsevier GmbH.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

A study of normoxic polymer gel using monomer 2-hydroxyethyl methacrylate (HEMA)

NASA Astrophysics Data System (ADS)

Ishak, Siti Atiqah; Mustafa, Iskandar Shahrim; Rahman, Azhar Abdul; Moktar, Mohd; Min, Ung Ngie

2015-04-01

The aim of this study is to determine the sensitivity of HEMA-polymer gel mixture consist of monomer 2-hydroxyethyl methacrylate (HEMA) with different types of composition. Several composition of HEMA-polymer gel were fabricated and the gels were irradiated with radiation dose between 10 cGy to 100cGy by using x-ray machine and 100 cGy to 1400 cGy by using 6 MV photon beam energy of linear accelerator. The degree of polymerization was evaluated by using magnetic resonance imaging (MRI) with dependence of R2-dose response. Polymer gel consists of cross-linker, anti-oxidant Tetrakis(Hydroxymethyl)phosphonium chloride solution (THPC) and oxygen scavenger hydroquinone shows a stable sensitivity with highest dose dependency. Besides, the results shows the stage polymerization consist of induction, propagation, termination, and chain transfer were dependence with type of chemical mixture and radiation dose. Thus, normoxic HEMA-polymer gel with the different gel formulations can have a better dose resolution and an appropriate recipe must be selected to increase of the sensitivity required and the stability of the dosimeter.

A study of normoxic polymer gel using monomer 2-hydroxyethyl methacrylate (HEMA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishak, Siti Atiqah; Mustafa, Iskandar Shahrim; Rahman, Azhar Abdul

2015-04-24

The aim of this study is to determine the sensitivity of HEMA-polymer gel mixture consist of monomer 2-hydroxyethyl methacrylate (HEMA) with different types of composition. Several composition of HEMA-polymer gel were fabricated and the gels were irradiated with radiation dose between 10 cGy to 100cGy by using x-ray machine and 100 cGy to 1400 cGy by using 6 MV photon beam energy of linear accelerator. The degree of polymerization was evaluated by using magnetic resonance imaging (MRI) with dependence of R2-dose response. Polymer gel consists of cross-linker, anti-oxidant Tetrakis(Hydroxymethyl)phosphonium chloride solution (THPC) and oxygen scavenger hydroquinone shows a stable sensitivitymore » with highest dose dependency. Besides, the results shows the stage polymerization consist of induction, propagation, termination, and chain transfer were dependence with type of chemical mixture and radiation dose. Thus, normoxic HEMA-polymer gel with the different gel formulations can have a better dose resolution and an appropriate recipe must be selected to increase of the sensitivity required and the stability of the dosimeter.« less

Fundamental study on the characteristics of a radiophotoluminescence glass dosemeter with no energy compensation filter for measuring patient entrance doses in cardiac interventional procedures.

PubMed

Kato, Mamoru; Chida, Koichi; Moritake, Takashi; Koguchi, Yasuhiro; Sato, Tadaya; Oosaka, Hajime; Tosa, Tetsuo; Kadowaki, Ken

2014-12-01

Cardiac interventional procedures have been increasing year by year. However, radiation skin injuries have been still reported. There is a necessity to measure the patient entrance skin dose (ESD), but an accurate dose measurement method has not been established. To measure the ESD, a lot of radiophotoluminescence dosemeters (RPLDs) provide an accurate measurement of the direct actual ESD at the points they are arrayed. The purpose of this study was to examine the characteristics of RPLD to measure the ESD. As a result, X-ray permeable RPLD (with no tin filter) did not interfere with the percutaneous coronary intervention procedure. The RPLD also had good fundamental performance characteristics. Although the RPLD had a little energy dependence, it showed excellent dose and dose-rate linearity, and good angular dependence. In conclusion, by calibrating the energy dependence, RPLDs are useful dosemeter to measure the ESD in cardiac intervention. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiation dosimeter

DOEpatents

Fox, Richard J.

1983-01-01

A radiation detector readout circuit is provided which produces a radiation dose-rate readout from a detector even though the detector output may be highly energy dependent. A linear charge amplifier including an output charge pump circuit amplifies the charge signal pulses from the detector and pumps the charge into a charge storage capacitor. The discharge rate of the capacitor through a resistor is controlled to provide a time-dependent voltage which when integrated provides an output proportional to the dose-rate of radiation detected by the detector. This output may be converted to digital form for readout on a digital display.

Radiation dosimeter

DOEpatents

Fox, R.J.

1981-09-01

A radiation detector readout circuit is provided which produces a radiation dose-rate readout from a detector even through the detector output may be highly energy dependent. A linear charge amplifier including an output charge pump circuit amplifies the charge signal pulses from the detector and pumps the charge into a charge storage capacitor. The discharge rate of the capacitor through a resistor is controlled to provide a time-dependent voltage which when integrated provides an output proportional to the dose-rate of radiation detected by the detector. This output may be converted to digital form for readout on a digital display.

Reactive oxygen species-based measurement of the dependence of the Coulomb nanoradiator effect on proton energy and atomic Z value.

PubMed

Seo, Seung-Jun; Jeon, Jae-Kun; Han, Sung-Mi; Kim, Jong-Ki

2017-11-01

The Coulomb nanoradiator (CNR) effect produces the dose enhancement effects from high-Z nanoparticles under irradiation with a high-energy ion beam. To gain insight into the radiation dose and biological significance of the CNR effect, the enhancement of reactive oxygen species (ROS) production from iron oxide or gold NPs (IONs or AuNPs, respectively) in water was investigated using traversing proton beams. The dependence of nanoradiator-enhanced ROS production on the atomic Z value and proton energy was investigated. Two biologically important ROS species were measured using fluorescent probes specific to •OH or [Formula: see text] in a series of water phantoms containing either AuNPs or IONs under irradiation with a 45- or 100-MeV proton beam. The enhanced generation of hydroxyl radicals (•OH) and superoxide anions ([Formula: see text]) was determined to be caused by the dependence on the NP concentration and proton energy. The proton-induced Au or iron oxide nanoradiators exhibited different ROS enhancement rates depending on the proton energy, suggesting that the CNR radiation varied. The curve of the superoxide anion production from the Au-nanoradiator showed strong non-linearity, unlike the linear behavior observed for hydroxyl radical production and the X-ray photoelectric nanoradiator. In addition, the 45-MeV proton-induced Au nanoradiator exhibited an ROS enhancement ratio of 8.54/1.50 ([Formula: see text] / •OH), similar to that of the 100-KeV X-ray photoelectric Au nanoradiator (7.68/1.46). The ROS-based detection of the CNR effect revealed its dependence on the proton beam energy, dose and atomic Z value and provided insight into the low-linear energy transfer (LET) CNR radiation, suggesting that these factors may influence the therapeutic efficacy via chemical reactivities, transport behaviors, and intracellular oxidative stress.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandervoort, E.; Szanto, J.; Christiansen, E.

Plastic scintillation dosimeters (PSDs) have favourable characteristics for small and composite field dosimetry in radiosurgery, however, imperfect corrections for the Cerenkov radiation contamination could limit their accuracy for complex deliveries. In this work, we characterize the dose and dose-rate linearity, directional dependence, and compare output factors with other stereotactic detectors for a new commercially available PSD (Exradin W1). We provide some preliminary comparisons of planned and measured dose for composite fields delivered clinically by a Cyberknife radiosurgery system. The W1 detector shows good linearity with dose (<0.5%) and dose rate (<0.8%) relative to the signal obtained using an ion chambermore » under the same conditions. A maximum difference of 2% was observed depending on the detector's angular orientation. Output factors for all detectors agree within a range of ±3.2% and ±1.5% for the 5 and 7.5 mm collimators, respectively, provided Monte-Carlo corrections for detector effects are applied to diode and ion chambers (without corrections the range is ±5.5% and ±3.1% for these two collimators). For clinical beam deliveries using 5 and 7.5 mm collimators, four of the six patients showed better agreement with planned dose for the PSD detector compared to a micro ion chamber. Two of the six patients investigated, however, showed 5% differences between PSD and planned dose, film measurements and the ratio of PSD and micro ion chamber signal suggest that further investigation is warranted for these plans. The W1 detector is a promising tool for stereotactic plan verification under the challenging dosimetric conditions of stereotactic radiosurgery.« less

Comparative evaluation of Kodak EDR2 and XV2 films for verification of intensity modulated radiation therapy.

PubMed

Dogan, Nesrin; Leybovich, Leonid B; Sethi, Anil

2002-11-21

Film dosimetry provides a convenient tool to determine dose distributions, especially for verification of IMRT plans. However, the film response to radiation shows a significant dependence on depth, energy and field size that compromise the accuracy of measurements. Kodak's XV2 film has a low saturation dose (approximately 100 cGy) and, consequently, a relatively short region of linear dose-response. The recently introduced Kodak extended range EDR2 film was reported to have a linear dose-response region extending to 500 cGy. This increased dose range may be particularly useful in the verification of IMRT plans. In this work, the dependence of Kodak EDR2 film's response on the depth, field size and energy was evaluated and compared with Kodak XV2 film. Co-60, 6 MV, 10 MV and 18 MV beams were used. Field sizes were 2 x 2, 6 x 6, 10 x 10, 14 x 14, 18 x 18 and 24 x 24 cm2. Doses for XV2 and EDR2 films were 80 cGy and 300 cGy, respectively. Optical density was converted to dose using depth-corrected sensitometric (Hurter and Driffield, or H&D) curves. For each field size, XV2 and EDR2 depth-dose curves were compared with ion chamber depth-dose curves. Both films demonstrated similar (within 1%) field size dependence. The deviation from the ion chamber for both films was small forthe fields ranging from 2 x 2 to 10 x 10 cm2: < or =2% for 6, 10 and 18 MV beams. No deviation was observed for the Co-60 beam. As the field size increased to 24 x 24 cm2, the deviation became significant for both films: approximately 7.5% for Co-60, approximately 5% for 6 MV and 10 MV, and approximately 6% for 18 MV. During the verification of IMRT plans, EDR2 film showed a better agreement with the calculated dose distributions than the XV2 film.

Sage Gene Expression Profiles Characterizing Cure

DTIC Science & Technology

2005-10-01

achieved in haematological malignancies. In addition, tumour cell lines showed a log-linear dose re- sponse when exposed to alkylating agents [26,27...direct carcinogen, N-methyl nitrosourea (NMU) and an indirect carcinogen, 7,12- dimethylbenzanthracene each depend upon the estrous cycle phase at the...a single dose of N-methyl-N- nitrosourea . Cancer Res 45: 3042–3047, 1995 8. Nagasawa H, Yanai R, Taniguchi H: Importance of mammary gland DNA synthesis

Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer.

PubMed

Zhu, L X; Waldren, C A; Vannias, D; Hei, T K

1996-03-01

Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer

NASA Technical Reports Server (NTRS)

Zhu, L. X.; Waldren, C. A.; Vannias, D.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

1996-01-01

Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

Dosimetric characteristics of a MOSFET dosimeter for clinical electron beams.

PubMed

Manigandan, D; Bharanidharan, G; Aruna, P; Devan, K; Elangovan, D; Patil, Vikram; Tamilarasan, R; Vasanthan, S; Ganesan, S

2009-09-01

The fundamental dosimetric characteristics of commercially available metal oxide semiconductor field effect transistor (MOSFET) detectors were studied for clinical electron beam irradiations. MOSFET showed excellent linearity against doses measured using an ion chamber in the dose range of 20-630cGy. MOSFET reproducibility is better at high doses compared to low doses. The output factors measured with the MOSFET were within +/-3% when compared with those measured with a parallel plate chamber. From 4 to 12MeV, MOSFETs showed a large angular dependence in the tilt directions and less in the axial directions. MOSFETs do not show any dose-rate dependence between 100 and 600MU/min. However, MOSFETs have shown under-response when the dose per pulse of the beam is decreased. No measurable effect in MOSFET response was observed in the temperature range of 23-40 degrees C. The energy dependence of a MOSFET dosimeter was within +/-3.0% for 6-18MeV electron beams and 5.5% for 4MeV ones. This study shows that MOSFET detectors are suitable for dosimetry of electron beams in the energy range of 4-18MeV.

Field size dependent mapping of medical linear accelerator radiation leakage

NASA Astrophysics Data System (ADS)

Vũ Bezin, Jérémi; Veres, Attila; Lefkopoulos, Dimitri; Chavaudra, Jean; Deutsch, Eric; de Vathaire, Florent; Diallo, Ibrahima

2015-03-01

The purpose of this study was to investigate the suitability of a graphics library based model for the assessment of linear accelerator radiation leakage. Transmission through the shielding elements was evaluated using the build-up factor corrected exponential attenuation law and the contribution from the electron guide was estimated using the approximation of a linear isotropic radioactive source. Model parameters were estimated by a fitting series of thermoluminescent dosimeter leakage measurements, achieved up to 100 cm from the beam central axis along three directions. The distribution of leakage data at the patient plane reflected the architecture of the shielding elements. Thus, the maximum leakage dose was found under the collimator when only one jaw shielded the primary beam and was about 0.08% of the dose at isocentre. Overall, we observe that the main contributor to leakage dose according to our model was the electron beam guide. Concerning the discrepancies between the measurements used to calibrate the model and the calculations from the model, the average difference was about 7%. Finally, graphics library modelling is a readily and suitable way to estimate leakage dose distribution on a personal computer. Such data could be useful for dosimetric evaluations in late effect studies.

Total Dose Effects on Single Event Transients in Linear Bipolar Systems

NASA Technical Reports Server (NTRS)

Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent

2008-01-01

Single Event Transients (SETs) originating in linear bipolar integrated circuits are known to undermine the reliability of electronic systems operating in the radiation environment of space. Ionizing particle radiation produces a variety of SETs in linear bipolar circuits. The extent to which these SETs threaten system reliability depends on both their shapes (amplitude and width) and their threshold energies. In general, SETs with large amplitudes and widths are the most likely to propagate from a bipolar circuit's output through a subsystem. The danger these SET pose is that, if they become latched in a follow-on circuit, they could cause an erroneous system response. Long-term exposure of linear bipolar circuits to particle radiation produces total ionizing dose (TID) and/or displacement damage dose (DDD) effects that are characterized by a gradual degradation in some of the circuit's electrical parameters. For example, an operational amplifier's gain-bandwidth product is reduced by exposure to ionizing radiation, and it is this reduction that contributes to the distortion of the SET shapes. In this paper, we compare SETs produced in a pristine LM124 operational amplifier with those produced in one exposed to ionizing radiation for three different operating configurations - voltage follower (VF), inverter with gain (IWG), and non-inverter with gain (NIWG). Each configuration produces a unique set of transient shapes that change following exposure to ionizing radiation. An important finding is that the changes depend on operating configuration; some SETs decrease in amplitude, some remain relatively unchanged, some become narrower and some become broader.

Relative Efficiency of TLD-100 to High Linear Energy Transfer Radiation: Correction to Astronaut Absorbed Dose

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cash, B. L.; Semones, E. J.; Yasuda, H.; Fujitaka, K.

1999-01-01

Response of thermoluminescent detectors (TLD-100) to high linear energy transfer (LET) particles has been studied using helium, carbon, silicon, and iron ions from the Heavy Ion Medical Accelerator at Chiba (Japan), iron ions from the Brookhaven National Laboratory (NY) Alternate Gradient Synchrotron, and 53, 134, 185, and 232 MeV protons from the Loma Linda accelerator. Using the measured relative (to 137Cs) dose efficiency, and measured LET spectra from a tissue equivalent proportional counter (TEPC) on 20 Space Shuttle flights, and 7 Mir flights, the underestimation of absorbed dose by these detectors has been evaluated. The dose underestimation is between 15-20% depending upon the flight inclination and shielding location. This has been confirmed by direct correlation of measured dose by TEPC and TLD-100 at a low shielded location in the Shuttle mid-deck. A comparison of efficiency- LET data with a compilation of similar data from TLD-700, shows that shapes of the two curves are nearly identical, but that the TLD-100 curve is systematically lower by about 13%, and is the major cause of dose underestimation. These results strongly suggest that TLDs used for crew dose estimation be regularly calibrated using heavy ions.

Relative Efficiency of TLD-100 to Linear Energy Transfer Radiation: Correction to Astronaut Absorbed Dose

NASA Technical Reports Server (NTRS)

Badhwar, Gautam D.; Cash, B. L.; Semones, E. J.; Yasuda, H.; Fujitaka, K.

1999-01-01

Response of thermoluminescent detectors (TLD-100) to high linear energy transfer (LET) particles has been studied using helium, carbon, silicon, and iron ions from the Heavy Ion Medical Accelerator at Chiba (Japan), iron ions from the Brookhaven National Laboratory (NY) Alternate Gradient Synchrotron, and 53, 134, 185, and 232 MeV protons from the Loma Linda accelerator. Using the measured relative (to (137)Cs dose efficiency, and measured LET spectra from a tissue equivalent proportional counter (TEPC) on 20 Space Shuttle flights, and 7 Mir flights, the underestimation of absorbed dose by these detectors has been evaluated. The dose underestimation is between 15-20% depending upon the flight inclination and shielding location. This has been confirmed by direct correlation of measured dose by TEPC and TLD-100 at a low shielded location in the Shuttle mid-deck. A comparison of efficiency- LET data with a compilation of similar data from TLD-700, shows that shapes of the two curves are nearly identical, but that the TLD-100 curve is systematically lower by about 13%, and is the major cause of dose underestimation. These results strongly suggest that TLDs used for crew dose estimation be regularly calibrated using heavy ions.

Plastic scintillation detectors for dose monitoring in digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Antunes, J.; Machado, J.; Peralta, L.; Matela, N.

2018-01-01

Plastic scintillators detectors (PSDs) have been studied as dosimeters, since they provide a cost-effective alternative to conventional ionization chambers. Measurement and analysis of energy dependency were performed on a Siemens Mammomat tomograph for two different peak kilovoltages: 26 kV and 35 kV. Both PSD displayed good linearity for each energy considered and almost no energy dependence.

Characterization of responses and comparison of calibration factor for commercial MOSFET detectors.

PubMed

Bharanidharan, Ganesan; Manigandan, Durai; Devan, Krishnamurthy; Subramani, Vellaiyan; Gopishankar, Natanasabapathi; Ganesh, Tharmar; Joshi, Rakeshchander; Rath, Gourakishore; Velmurugan, Jagadeesan; Aruna, Prakasarao; Ganesan, Singaravelu

2005-01-01

A commercial metal oxide silicon field effect transistor (MOSFET) dosimeter of model TN502-RD has been characterized for its linearity, reproducibility, field size dependency, dose rate dependency, and angular dependency for Cobalt-60 (60Co), 6-MV, and 15-MV beam energies. The performance of the MOSFET clearly shows that it is highly reproducible, independent of field size and dose rate. Furthermore, MOSFET has a very high degree of linearity, with r-value>0.9 for all 3 energies. The calibration factor for 2 similar MOSFET detectors of model TN502-RD were also estimated and compared for all 3 energies. The calibration factor between the 2 similar MOSFET detectors shows a variation of about 1.8% for 60Co and 15 MV, and for 6 MV it shows variation of about 2.5%, indicating that calibration should be done whenever a new MOSFET is used. However, the detector shows considerable angular dependency of about 8.8% variation. This may be due to the variation in radiation sensitivity between flat and bubble sides of the MOSFET, and indicates that positional care must be taken while using MOSFET for stereotactic radiosurgery and stereotactic radiotherapy dosimetric applications.

Effect of americium-241 alpha-particles on the dose-response of chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization.

PubMed

Barquinero, J F; Stephan, G; Schmid, E

2004-02-01

To evaluate by the fluorescent in-situ hybridization (FISH) technique the dose-response and intercellular distribution of alpha-particle-induced chromosome aberrations. In particular, the validity of using the yield of characteristic types of chromosome abnormalities in stable cells as quantitative indicators for retrospective dose reconstruction has been evaluated. Monolayers of human peripheral lymphocytes were exposed at doses from 0.02 to 1 Gy to alpha-particles emitted from a source of americium-241. The most probable energy of the alpha-particles entering the cells was 2.7 MeV. FISH painting was performed using DNA probes for chromosomes 2, 4 and 8 in combination with a pan-centromeric probe. In complete first-division cells, identified by harlequin staining, aberrations involving painted target chromosomal material were recorded as well as aberrations involving only unpainted chromosomal material. In total, the percentage of complex aberrations was about 35% and no dose dependence was observed. When complex-type exchanges were reduced to simple base types, the different cell distributions were clearly over-dispersed, and the linear coefficients of the dose-effect curves for translocations were significantly higher than for dicentrics. For past dose reconstruction, only a few complex aberrations were in stable cells. The linear coefficient obtained for transmissible aberrations in stable cells was more than seven times lower than that obtained in all analysed cells, i.e. including unstable cells. FISH-based analysis of complex rearrangements allows discrimination between partial-body exposures to low-linear energy transfer radiation and high-linear energy transfer exposures. In assessing past or chronic exposure to alpha-particles, the use of a dose-effect curve obtained by FISH-based translocation data, which had not excluded data determined in unstable cells, would underestimate the dose. Insertions are ineffective biomarkers because their frequency is too low.

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs

PubMed Central

Burr, David B.; Liu, Ziyue; Allen, Matthew R.

2014-01-01

Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than bone’s material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of femoral cortical bone in humans. PMID:25445446

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

SU-G-201-17: Verification of Dose Distributions From High-Dose-Rate Brachytherapy Ir-192 Source Using a Multiple-Array-Diode-Detector (MapCheck2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harpool, K; De La Fuente Herman, T; Ahmad, S

Purpose: To investigate quantitatively the accuracy of dose distributions for the Ir-192 high-dose-rate (HDR) brachytherapy source calculated by the Brachytherapy-Planning system (BPS) and measured using a multiple-array-diode-detector in a heterogeneous medium. Methods: A two-dimensional diode-array-detector system (MapCheck2) was scanned with a catheter and the CT-images were loaded into the Varian-Brachytherapy-Planning which uses TG-43-formalism for dose calculation. Treatment plans were calculated for different combinations of one dwell-position and varying irradiation times and different-dwell positions and fixed irradiation time with the source placed 12mm from the diode-array plane. The calculated dose distributions were compared to the measured doses with MapCheck2 delivered bymore » an Ir-192-source from a Nucletron-Microselectron-V2-remote-after-loader. The linearity of MapCheck2 was tested for a range of dwell-times (2–600 seconds). The angular effect was tested with 30 seconds irradiation delivered to the central-diode and then moving the source away in increments of 10mm. Results: Large differences were found between calculated and measured dose distributions. These differences are mainly due to absence of heterogeneity in the dose calculation and diode-artifacts in the measurements. The dose differences between measured and calculated due to heterogeneity ranged from 5%–12% depending on the position of the source relative to the diodes in MapCheck2 and different heterogeneities in the beam path. The linearity test of the diode-detector showed 3.98%, 2.61%, and 2.27% over-response at short irradiation times of 2, 5, and 10 seconds, respectively, and within 2% for 20 to 600 seconds (p-value=0.05) which depends strongly on MapCheck2 noise. The angular dependency was more pronounced at acute angles ranging up to 34% at 5.7 degrees. Conclusion: Large deviations between measured and calculated dose distributions for HDR-brachytherapy with Ir-192 may be improved when considering medium heterogeneity and dose-artifact of the diodes. This study demonstrates that multiple-array-diode-detectors provide practical and accurate dosimeter to verify doses delivered from the brachytherapy Ir-192-source.« less

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PubMed

Karsch, L; Beyreuther, E; Burris-Mog, T; Kraft, S; Richter, C; Zeil, K; Pawelke, J

2012-05-01

The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karsch, L.; Beyreuther, E.; Burris-Mog, T.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10{sup 11} Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the numbermore » of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410{sup 9} Gy/s within 2% (OSL and TLD) and up to 1510{sup 9} Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.« less

SU-E-T-120: Dosimetric Characteristics Study of NanoDotâ,,¢ for In-Vivo Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussain, A; Wasaye, A; Gohar, R

Purpose: The purpose of the study was to analyze the dosimetric characteristics (energy dependence, reproducibility and dose linearity) of nanoDot™ optically stimulated luminescence dosimeters (OSLDs) and validate their potential use during in-vivo dosimetry, specifically TBI. The manufacturer stated accuracy is ±10% for standard nanoDot™. Methods: At AKUH, the InLight microStar OSL dosimetry system for patient in-vivo dosimetry is in use since 2012. Twenty-five standard nanoDot™ were used in the analysis. Sensitivity and reproducibility was tested in the first part with 6MV and 18 MV Varian x-ray beams. Each OSLD was irradiated to 100cGy dose at nominal SSD (100 cm). Allmore » the OSLDs were read 3 times for average reading. Dose linearity and calibration were also performed with same beams in common clinical dose range of 0 - 500 cGy. In addition, verification of TBI absolute dose at extended SSD (500cm) was also performed. Results: The reproducibility observed with the OSLD was better than the manufacturer stated limits. Measured doses vary less than ±2% in 19(76%) OSLDs, whereas less than ±3% in 6(24%) OSLDs. Their sensitivity was approximately 525 counts per cGy. Better agreement was observed between measurements, with a standard deviation of 1.8%. A linear dose response was observed with OSLDs for both 6 and 18MV beams in 0 - 500 cGy dose range. TBI measured doses at 500 cm SSD were also confirmed to be within ±0.5% and ±1.3% of the ion chamber measured doses for 6 and 18MV beams respectively. Conclusion: The dosimetric results demonstrate that nanoDot™ can be potentially used for in-vivo dosimetry verification in various clinical situations, with a high degree of accuracy and precision. In addition OSLDs exhibit better dose reproducibility with standard deviation of 1.8%. There was no significant difference in their response to 6 and 18MV beams. The dose response was also linear.« less

Clinical application of the OneDose Patient Dosimetry System for total body irradiation.

PubMed

Best, S; Ralston, A; Suchowerska, N

2005-12-21

The OneDose Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Validation of a MOSFET dosemeter system for determining the absorbed and effective radiation doses in diagnostic radiology.

PubMed

Manninen, A-L; Kotiaho, A; Nikkinen, J; Nieminen, M T

2015-04-01

This study aimed to validate a MOSFET dosemeter system for determining absorbed and effective doses (EDs) in the dose and energy range used in diagnostic radiology. Energy dependence, dose linearity and repeatability of the dosemeter were examined. The absorbed doses (ADs) were compared at anterior-posterior projection and the EDs were determined at posterior-anterior, anterior-posterior and lateral projections of thoracic imaging using an anthropomorphic phantom. The radiation exposures were made using digital radiography systems. This study revealed that the MOSFET system with high sensitivity bias supply set-up is sufficiently accurate for AD and ED determination. The dosemeter is recommended to be calibrated for energies <60 and >80 kVp. The entrance skin dose level should be at least 5 mGy to minimise the deviation of the individual dosemeter dose. For ED determination, dosemeters should be implanted perpendicular to the surface of the phantom to prevent the angular dependence error. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of TLD-100 micro-cubes for use in small field dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peña-Jiménez, Salvador, E-mail: zoid-9861@yahoo.com.mx; Gamboa-deBuen, Isabel, E-mail: gamboa@nucleares.unam.mx; Lárraga-Gutiérrez, José Manuel, E-mail: jose.larraga.gtz@gmail.com, E-mail: amanda.garcia.g@gmail.com

At present there are no international regulations for the management of millimeter scale fields and there are no suggestions for a reference detector to perform the characterization and dose determination for unconventional radiation beams (small fields) so that the dosimetry of small fields remains an open research field worldwide because these fields are used in radiotherapy treatments. Sensitivity factors and reproducibility of TLD-100 micro-cubes (1×1×1 mm3) were determinate irradiating the dosimeters with a 6 MV beam in a linear accelerator dedicated to radiosurgery at the Instituto Nacional de Neurología y Neurocirugía (INNN). Thermoluminescent response as a function of dose wasmore » determined for doses in water between 0.5 and 3 Gy and two field sizes (2×2 cm2 and 10×10 cm2). It was found that the response is linear over the dose range studied and it does not depend on field size.« less

Observations on personnel dosimetry for radiotherapy personnel operating high-energy LINACs.

PubMed

Glasgow, G P; Eichling, J; Yoder, R C

1986-06-01

A series of measurements were conducted to determine the cause of a sudden increase in personnel radiation exposures. One objective of the measurements was to determine if the increases were related to changing from film dosimeters exchanged monthly to TLD-100 dosimeters exchanged quarterly. While small increases were observed in the dose equivalents of most employees, the dose equivalents of personnel operating medical electron linear accelerators with energies greater than 20 MV doubled coincidentally with the change in the personnel dosimeter program. The measurements indicated a small thermal neutron radiation component around the accelerators operated by these personnel. This component caused the doses measured with the TLD-100 dosimeters to be overstated. Therefore, the increase in these personnel dose equivalents was not due to changes in work habits or radiation environments. Either film or TLD-700 dosimeters would be suitable for personnel monitoring around high-energy linear accelerators. The final choice would depend on economics and personal preference.

Characterization of TLD-100 micro-cubes for use in small field dosimetry

NASA Astrophysics Data System (ADS)

Peña-Jiménez, Salvador; Lárraga-Gutiérrez, José Manuel; García-Garduño, Olivia Amanda; Gamboa-deBuen, Isabel

2014-11-01

At present there are no international regulations for the management of millimeter scale fields and there are no suggestions for a reference detector to perform the characterization and dose determination for unconventional radiation beams (small fields) so that the dosimetry of small fields remains an open research field worldwide because these fields are used in radiotherapy treatments. Sensitivity factors and reproducibility of TLD-100 micro-cubes (1×1×1 mm3) were determinate irradiating the dosimeters with a 6 MV beam in a linear accelerator dedicated to radiosurgery at the Instituto Nacional de Neurología y Neurocirugía (INNN). Thermoluminescent response as a function of dose was determined for doses in water between 0.5 and 3 Gy and two field sizes (2×2 cm2 and 10×10 cm2). It was found that the response is linear over the dose range studied and it does not depend on field size.

Carbon Ion Irradiation of the Rat Spinal Cord: Dependence of the Relative Biological Effectiveness on Linear Energy Transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saager, Maria, E-mail: m.saager@dkfz.de; Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg; Glowa, Christin

2014-09-01

Purpose: To measure the relative biological effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET). Methods and Materials: As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD{sub 50} values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD{sub 50} for photons of our previous study. Results:more » Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD{sub 50} values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm. Conclusions: The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning.« less

Agreement between gamma passing rates using computed tomography in radiotherapy and secondary cancer risk prediction from more advanced dose calculated models

PubMed Central

Balosso, Jacques

2017-01-01

Background During the past decades, in radiotherapy, the dose distributions were calculated using density correction methods with pencil beam as type ‘a’ algorithm. The objectives of this study are to assess and evaluate the impact of dose distribution shift on the predicted secondary cancer risk (SCR), using modern advanced dose calculation algorithms, point kernel, as type ‘b’, which consider change in lateral electrons transport. Methods Clinical examples of pediatric cranio-spinal irradiation patients were evaluated. For each case, two radiotherapy treatment plans with were generated using the same prescribed dose to the target resulting in different number of monitor units (MUs) per field. The dose distributions were calculated, respectively, using both algorithms types. A gamma index (γ) analysis was used to compare dose distribution in the lung. The organ equivalent dose (OED) has been calculated with three different models, the linear, the linear-exponential and the plateau dose response curves. The excess absolute risk ratio (EAR) was also evaluated as (EAR = OED type ‘b’ / OED type ‘a’). Results The γ analysis results indicated an acceptable dose distribution agreement of 95% with 3%/3 mm. Although, the γ-maps displayed dose displacement >1 mm around the healthy lungs. Compared to type ‘a’, the OED values from type ‘b’ dose distributions’ were about 8% to 16% higher, leading to an EAR ratio >1, ranged from 1.08 to 1.13 depending on SCR models. Conclusions The shift of dose calculation in radiotherapy, according to the algorithm, can significantly influence the SCR prediction and the plan optimization, since OEDs are calculated from DVH for a specific treatment. The agreement between dose distribution and SCR prediction depends on dose response models and epidemiological data. In addition, the γ passing rates of 3%/3 mm does not translate the difference, up to 15%, in the predictions of SCR resulting from alternative algorithms. Considering that modern algorithms are more accurate, showing more precisely the dose distributions, but that the prediction of absolute SCR is still very imprecise, only the EAR ratio could be used to rank radiotherapy plans. PMID:28811995

Application of commercial MOSFET detectors for in vivo dosimetry in the therapeutic x-ray range from 80 kV to 250 kV

NASA Astrophysics Data System (ADS)

Ehringfeld, Christian; Schmid, Susanne; Poljanc, Karin; Kirisits, Christian; Aiginger, Hannes; Georg, Dietmar

2005-01-01

The purpose of this study was to investigate the dosimetric characteristics (energy dependence, linearity, fading, reproducibility, etc) of MOSFET detectors for in vivo dosimetry in the kV x-ray range. The experience of MOSFET in vivo dosimetry in a pre-clinical study using the Alderson phantom and in clinical practice is also reported. All measurements were performed with a Gulmay D3300 kV unit and TN-502RDI MOSFET detectors. For the determination of correction factors different solid phantoms and a calibrated Farmer-type chamber were used. The MOSFET signal was linear with applied dose in the range from 0.2 to 2 Gy for all energies. Due to fading it is recommended to read the MOSFET signal during the first 15 min after irradiation. For long time intervals between irradiation and readout the fading can vary largely with the detector. The temperature dependence of the detector signal was small (0.3% °C-1) in the temperature range between 22 and 40 °C. The variation of the measuring signal with beam incidence amounts to ±5% and should be considered in clinical applications. Finally, for entrance dose measurements energy-dependent calibration factors, correction factors for field size and irradiated cable length were applied. The overall accuracy, for all measurements, was dominated by reproducibility as a function of applied dose. During the pre-clinical in vivo study, the agreement between MOSFET and TLD measurements was well within 3%. The results of MOSFET measurements, to determine the dosimetric characteristics as well as clinical applications, showed that MOSFET detectors are suitable for in vivo dosimetry in the kV range. However, some energy-dependent dosimetry effects need to be considered and corrected for. Due to reproducibility effects at low dose levels accurate in vivo measurements are only possible if the applied dose is equal to or larger than 2 Gy.

Application of commercial MOSFET detectors for in vivo dosimetry in the therapeutic x-ray range from 80 kV to 250 kV.

PubMed

Ehringfeld, Christian; Schmid, Susanne; Poljanc, Karin; Kirisits, Christian; Aiginger, Hannes; Georg, Dietmar

2005-01-21

The purpose of this study was to investigate the dosimetric characteristics (energy dependence, linearity, fading, reproducibility, etc) of MOSFET detectors for in vivo dosimetry in the kV x-ray range. The experience of MOSFET in vivo dosimetry in a pre-clinical study using the Alderson phantom and in clinical practice is also reported. All measurements were performed with a Gulmay D3300 kV unit and TN-502RDI MOSFET detectors. For the determination of correction factors different solid phantoms and a calibrated Farmer-type chamber were used. The MOSFET signal was linear with applied dose in the range from 0.2 to 2 Gy for all energies. Due to fading it is recommended to read the MOSFET signal during the first 15 min after irradiation. For long time intervals between irradiation and readout the fading can vary largely with the detector. The temperature dependence of the detector signal was small (0.3% degrees C(-1)) in the temperature range between 22 and 40 degrees C. The variation of the measuring signal with beam incidence amounts to +/-5% and should be considered in clinical applications. Finally, for entrance dose measurements energy-dependent calibration factors, correction factors for field size and irradiated cable length were applied. The overall accuracy, for all measurements, was dominated by reproducibility as a function of applied dose. During the pre-clinical in vivo study, the agreement between MOSFET and TLD measurements was well within 3%. The results of MOSFET measurements, to determine the dosimetric characteristics as well as clinical applications, showed that MOSFET detectors are suitable for in vivo dosimetry in the kV range. However, some energy-dependent dosimetry effects need to be considered and corrected for. Due to reproducibility effects at low dose levels accurate in vivo measurements are only possible if the applied dose is equal to or larger than 2 Gy.

Effect of processor temperature on film dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

Optically stimulated luminescence (OSL) of carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for film dosimetry in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schembri, V.; Heijmen, B. J. M.

2007-06-15

Introduction and Purpose: Conventional x-ray films and radiochromic films have inherent challenges for high precision radiotherapy dosimetry. Here we have investigated basic characteristics of optically stimulated luminescence (OSL) of irradiated films containing carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for dosimetry in therapeutic photon and electron beams. Materials and Methods: The OSL films consist of a polystyrene sheet, with a top layer of a mixture of single crystals of Al{sub 2}O{sub 3}:C, ground into a powder, and a polyester base. The total thickness of the films is 0.3 mm. Measurements have been performed in a water equivalent phantom, using 4, 6,more » 10, and 18 MV photon beams, and 6-22 MeV electron beams. The studies include assessment of the film response (acquired OSL signal/delivered dose) on delivered dose (linearity), dose rate (1-6 Gy/min), beam quality, field size and depth (6 MV, ranges 4x4-30x30 cm{sup 2}, d{sub max}-35 cm). Doses have been derived from ionization chamber measurements. OSL films have also been compared with conventional x-ray and GafChromic films for dosimetry outside the high dose area, with a high proportion of low dose scattered photons. In total, 787 OSL films have been irradiated. Results: Overall, the OSL response for electron beams was 3.6% lower than for photon beams. Differences between the various electron beam energies were not significant. The 6 and 18 MV photon beams differed in response by 4%. No response dependencies on dose rate were observed. For the 6 MV beam, the field size and depth dependencies of the OSL response were within {+-}2.5%. The observed inter-film response variation for films irradiated with the same dose varied from 1% to 3.2% (1 SD), depending on the measurement day. At a depth of 20 cm, 5 cm outside the 20x20 cm{sup 2} 6 and 18 MV beams, an over response of 17% was observed. In contrast to GafChromic and conventional x-ray films, the response of the Al{sub 2}O{sub 3}:C films is linear in the clinically relevant dose range 0-200 cGy. Conclusions: Measurement of the OSL signal of irradiated films containing Al{sub 2}O{sub 3}:C is a promising technique for film dosimetry in radiotherapy with no or small response variations with dose rate, beam quality, field size and depth, and a linear response from 0 to 200 cGy.« less

Photoluminescence of radiation-induced color centers in lithium fluoride thin films for advanced diagnostics of proton beams

NASA Astrophysics Data System (ADS)

Piccinini, M.; Ambrosini, F.; Ampollini, A.; Picardi, L.; Ronsivalle, C.; Bonfigli, F.; Libera, S.; Nichelatti, E.; Vincenti, M. A.; Montereali, R. M.

2015-06-01

Systematic irradiation of thermally evaporated 0.8 μm thick polycrystalline lithium fluoride films on glass was performed by proton beams of 3 and 7 MeV energies, produced by a linear accelerator, in a fluence range from 1011 to 1015 protons/cm2. The visible photoluminescence spectra of radiation-induced F2 and F3+ laser active color centers, which possess almost overlapping absorption bands at about 450 nm, were measured under laser pumping at 458 nm. On the basis of simulations of the linear energy transfer with proton penetration depth in LiF, it was possible to obtain the behavior of the measured integrated photoluminescence intensity of proton irradiated LiF films as a function of the deposited dose. The photoluminescence signal is linearly dependent on the deposited dose in the interval from 103 to about 106 Gy, independently from the used proton energies. This behavior is very encouraging for the development of advanced solid state radiation detectors based on optically transparent LiF thin films for proton beam diagnostics and two-dimensional dose mapping.

Dosimetric Accuracy of a Dual Photon Energy Linac at Low Monitor Setting for Various Pulse Repetition Frequencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Anil Kumar; Supe, Sanjay S.; Anantha, N.

2015-01-15

Accuracy of dose delivery at low monitor unit setting is studied for a dual photon energy linear accelerator. Dose delivered per MU is found to be constant for both the photon beams for MU settings above 30. For lower MUs there is definite deviation from the calibrated value and the error is found to be increasing as fewer MUs are set for dose delivery. This dose/MU ratio at low MU setting is found to be dose-rate dependent, showing an increasing trend with pulse repetition frequency (PRF). Also, the dosimetric ratio is observed to be mode dependent; its value for anmore » 18 MV beam is almost double that observed in the case of a 6 MV beam at very low MU setting. The magnitude of this error should be determined for each energy so that appropriate corrections can be applied if very low MUs are to be used.« less

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter

In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicronmore » level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches that provides a testable biological mechanism (i.e., RIF). In addition, we propose that DSB pairing will help develop more accurate alternatives to the linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.« less

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

PubMed

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance characteristics of the EPR dosimetry system with table sugar in radiotherapy applications.

PubMed

Mikou, M; Ghosne, N; El Baydaoui, R; Zirari, Z; Kuntz, F

2015-05-01

Performance characteristics of the megavoltage photon dose measurements with EPR and table sugar were analyzed. An advantage of sugar as a dosimetric material is its tissue equivalency. The minimal detectable dose was found to be 1.5Gy for both the 6 and 18MV photons. The dose response curves are linear up to at least 20Gy. The energy dependence of the dose response in the megavoltage energy range is very weak and probably statistically insignificant. Reproducibility of measurements of various doses in this range performed with the peak-to-peak and double-integral methods is reported. The method can be used in real-time dosimetry in radiation therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low dose ionizing radiation detection using conjugated polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, E.A.B.; Borin, J.F.; Nicolucci, P.

2005-03-28

In this work, the effect of gamma radiation on the optical properties of poly[2-methoxy-5-(2{sup '}-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) is studied. The samples were irradiated at room temperature with different doses from 0 Gy to 152 Gy using a {sup 60}Co gamma ray source. For thin films, significant changes in the UV-visible spectra were only observed at high doses (>1 kGy). In solution, shifts in absorption peaks are observed at low doses (<10 Gy), linearly dependent on dose. The shifts are explained by conjugation reduction, and possible causes are discussed. Our results indicate that MEH-PPV solution can be used as a dosimeter adequatemore » for medical applications.« less

SEMICONDUCTOR TECHNOLOGY: An efficient dose-compensation method for proximity effect correction

NASA Astrophysics Data System (ADS)

Ying, Wang; Weihua, Han; Xiang, Yang; Renping, Zhang; Yang, Zhang; Fuhua, Yang

2010-08-01

A novel simple dose-compensation method is developed for proximity effect correction in electron-beam lithography. The sizes of exposed patterns depend on dose factors while other exposure parameters (including accelerate voltage, resist thickness, exposing step size, substrate material, and so on) remain constant. This method is based on two reasonable assumptions in the evaluation of the compensated dose factor: one is that the relation between dose factors and circle-diameters is linear in the range under consideration; the other is that the compensated dose factor is only affected by the nearest neighbors for simplicity. Four-layer-hexagon photonic crystal structures were fabricated as test patterns to demonstrate this method. Compared to the uncorrected structures, the homogeneity of the corrected hole-size in photonic crystal structures was clearly improved.

[Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

PubMed

Koterov, A N; Ushenkova, L N; Biryukov, A P

2016-01-01

On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly reduce the strength of associations for RET/PTC in total. On the basis of ordinal scale doses (background, "low" (0.1 Gy), "middle" (0.1-1 Gy) and "large" (1-10 Gy) dose) also found was a significant correlation (Spearman) with the dose for the frequency RET/PTC in total (r = 0.736; p = 0.0098), but for certain types of rearrangements the results were reverse to the previous analysis (the effect was significant only for the RET/PTC3: r = 0.731; p = 0.024). The linear dose-response trends of the Cochrane-Armitage-test for the frequency of RET/PTC in total, RET/PTC1 and RET/PTC3 depending on the dose to the thyroid in the ordinal scale were registered (p, respectively: < 0.0001 < 0.0001 and 0.007). Thus; after more than 20 years of the molecular and epidemiological research of RET/PTC in thyroid radiogenic carcinomas the comprehensive evidence of the dose-effect dependence existence indicating a real relationship between the studied parameters and a radiation factor was obtained for the first time.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to testmore » the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.« less

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, R. M.; Silosky, M., E-mail: michael.silosky@ucdenver.edu

Purpose: The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. Methods: This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position themore » dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. Results: (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R{sup 2} = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o’clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. Conclusions: (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.« less

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits.

PubMed

Marsh, R M; Silosky, M

2015-04-01

The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position the dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R(2) = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o'clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.

Evaluation of characteristics of high-energy electron beams using N-isopropyl-acrylamide gel dosimeter

NASA Astrophysics Data System (ADS)

Shih, Tian-Yu; Yen, Tsung-Hsien; Liu, Yan-Lin; Luzhbin, Dmytro; Wu, Jay

2017-11-01

The advantage of electron beam radiotherapy is that the absorbed dose rapidly decreases with the increasing depth, which can prevent damage to deeper organs and tissues. Accurately evaluating the absorbed dose in the superficial tumor is imperative. This study assessed the characteristics of electron beams by using the N-isopropyl-acrylamide (n-NIPAM) gel dosimeter. The n-NIPAM gel was composed of 6% gelatin, 5% monomer, and 2.5% cross-linker with 5 mM tetrakis (hydroxymethyl) phosphonium chloride for deoxygenation. The gel was irradiated with 6-, 9-, and 12-MeV electron beams with dose rates of 100-600 MU/min, respectively. The energy dependence and dose rate dependence were assessed. The beam profiles and percentage depth doses were measured and compared with the results of the Gafchromic film and ionization chamber. The linearity of the n-NIPAM gel under 6-, 9-, and 12-MeV electrons was larger than 0.990 with 2% variation in sensitivity. The sensitivity of the gel under 100-600 MU/min showed 5% variations. The energy and dose rate dependence can be negligible. The beam profiles and percentage depth doses measured by the n-NIPAM gel matched well with the results of the ionization chamber and film. This study reveals the possibility of using the n-NIPAM gel dosimeter for electron beam measurements in clinical radiotherapy.

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

Characterization of a novel two dimensional diode array the "magic plate" as a radiation detector for radiation therapy treatment.

PubMed

Wong, J H D; Fuduli, I; Carolan, M; Petasecca, M; Lerch, M L F; Perevertaylo, V L; Metcalfe, P; Rosenfeld, A B

2012-05-01

Intensity modulated radiation therapy (IMRT) utilizes the technology of multileaf collimators to deliver highly modulated and complex radiation treatment. Dosimetric verification of the IMRT treatment requires the verification of the delivered dose distribution. Two dimensional ion chamber or diode arrays are gaining popularity as a dosimeter of choice due to their real time feedback compared to film dosimetry. This paper describes the characterization of a novel 2D diode array, which has been named the "magic plate" (MP). It was designed to function as a 2D transmission detector as well as a planar detector for dose distribution measurements in a solid water phantom for the dosimetric verification of IMRT treatment delivery. The prototype MP is an 11 × 11 detector array based on thin (50 μm) epitaxial diode technology mounted on a 0.6 mm thick Kapton substrate using a proprietary "drop-in" technology developed by the Centre for Medical Radiation Physics, University of Wollongong. A full characterization of the detector was performed, including radiation damage study, dose per pulse effect, percent depth dose comparison with CC13 ion chamber and build up characteristics with a parallel plane ion chamber measurements, dose linearity, energy response and angular response. Postirradiated magic plate diodes showed a reproducibility of 2.1%. The MP dose per pulse response decreased at higher dose rates while at lower dose rates the MP appears to be dose rate independent. The depth dose measurement of the MP agrees with ion chamber depth dose measurements to within 0.7% while dose linearity was excellent. MP showed angular response dependency due to the anisotropy of the silicon diode with the maximum variation in angular response of 10.8% at gantry angle 180°. Angular dependence was within 3.5% for the gantry angles ± 75°. The field size dependence of the MP at isocenter agrees with ion chamber measurement to within 1.1%. In the beam perturbation study, the surface dose increased by 12.1% for a 30 × 30 cm(2) field size at the source to detector distance (SDD) of 80 cm whilst the transmission for the MP was 99%. The radiation response of the magic plate was successfully characterized. The array of epitaxial silicon based detectors with "drop-in" packaging showed properties suitable to be used as a simplified multipurpose and nonperturbing 2D radiation detector for radiation therapy dosimetric verification.

A diffusion-free and linear-energy-transfer-independent nanocomposite Fricke gel dosimeter

NASA Astrophysics Data System (ADS)

Maeyama, T.; Fukunishi, N.; Ishikawa, K. L.; Furuta, T.; Fukasaku, K.; Takagi, S.; Noda, S.; Himeno, R.; Fukuda, S.

2014-03-01

We report a new magnetic-resonance-imaging (MRI) based nanocomposite Fricke gel (NC-FG) dosimeter system, which is free from two main drawbacks of conventional Fricke gel dosimeters, namely, the diffusion of the radiation products and the linear-energy-transfer (LET) dependence of the radiation sensitivity when used for ion beams. The NC-FG dosimeter was prepared by incorporating 1% (w/w) clay nanoparticles into deaerated Fricke gel. We have dosimetrically characterized the NC-FG by using MRI measurements after irradiation with a monoenergetic 290 MeV/nucleon carbon beam. No diffusion of the radiation products was observed during nine days after the irradiation. Moreover, its response faithfully reproduced the depth-dose distribution measured by an ionization chamber, which indicates the absence of the LET dependence. Also, the NC-FG dosimeter exhibited a good linearity up to 800 Gy.

Characterization and clinical evaluation of a novel 2D detector array for conventional and flattening filter free (FFF) IMRT pre-treatment verification.

PubMed

Sekar, Yuvaraj; Thoelking, Johannes; Eckl, Miriam; Kalichava, Irakli; Sihono, Dwi Seno Kuncoro; Lohr, Frank; Wenz, Frederik; Wertz, Hansjoerg

2018-04-01

The novel MatriXX FFF (IBA Dosimetry, Germany) detector is a new 2D ionization chamber detector array designed for patient specific IMRT-plan verification including flattening-filter-free (FFF) beams. This study provides a detailed analysis of the characterization and clinical evaluation of the new detector array. The verification of the MatriXX FFF was subdivided into (i) physical dosimetric tests including dose linearity, dose rate dependency and output factor measurements and (ii) patient specific IMRT pre-treatment plan verifications. The MatriXX FFF measurements were compared to the calculated dose distribution of a commissioned treatment planning system by gamma index and dose difference evaluations for 18 IMRT-sequences. All IMRT-sequences were measured with original gantry angles and with collapsing all beams to 0° gantry angle to exclude the influence of the detector's angle dependency. The MatriXX FFF was found to be linear and dose rate independent for all investigated modalities (deviations ≤0.6%). Furthermore, the output measurements of the MatriXX FFF were in very good agreement to reference measurements (deviations ≤1.8%). For the clinical evaluation an average pixel passing rate for γ (3%,3mm) of (98.5±1.5)% was achieved when applying a gantry angle correction. Also, with collapsing all beams to 0° gantry angle an excellent agreement to the calculated dose distribution was observed (γ (3%,3mm) =(99.1±1.1)%). The MatriXX FFF fulfills all physical requirements in terms of dosimetric accuracy. Furthermore, the evaluation of the IMRT-plan measurements showed that the detector particularly together with the gantry angle correction is a reliable device for IMRT-plan verification including FFF. Copyright © 2017. Published by Elsevier GmbH.

Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

2003-01-01

The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

Effects of irradiation source and dose level on quality characteristics of processed meat products

NASA Astrophysics Data System (ADS)

Ham, Youn-Kyung; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Choi, Yun-Sang; Song, Beom-Seok; Park, Jong-Heum; Kim, Cheon-Jei

2017-01-01

The effect of irradiation source (gamma-ray, electron-beam, and X-ray) and dose levels on the physicochemical, organoleptic and microbial properties of cooked beef patties and pork sausages was studied, during 10 days of storage at 30±1 °C. The processed meat products were irradiated at 0, 2.5, 5, 7.5, and 10 kGy by three different irradiation sources. The pH of cooked beef patties and pork sausages was unaffected by irradiation sources or their doses. The redness of beef patties linearly decreased with increasing dose level (P<0.05), obviously by e-beam irradiation compared to gamma-ray and X-ray (P<0.05). The redness of pork sausages was increased by gamma-ray irradiation, whereas it decreased by e-beam irradiation depending on absorbed dose level. No significant changes in overall acceptability were observed for pork sausages regardless of irradiation source (P>0.05), while gamma-ray irradiated beef patties showed significantly decreased overall acceptability in a dose-dependent manner (P<0.05). Lipid oxidation of samples was accelerated by irradiation depending on irradiation sources and dose levels during storage at 30 °C. E-beam reduced total aerobic bacteria of beef patties more effectively, while gamma-ray considerably decreased microbes in pork sausages as irradiation dose increased. The results of this study indicate that quality attributes of meat products, in particular color, lipid oxidation, and microbial properties are significantly influenced by the irradiation sources.

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

PubMed Central

Ding, Defang; Zhang, Yaping; Wang, Jing; Wang, Xufei; Fan, Dunhuang; He, Linfeng; Zhang, Xuxia; Gao, Yun; Li, Qiang; Chen, Honghong

2016-01-01

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

Total target volume is a better predictor of whole brain dose from gamma stereotactic radiosurgery than the number, shape, or location of the lesions

PubMed Central

Narayanasamy, Ganesh; Smith, Adam; Van Meter, Emily; McGarry, Ronald; Molloy, Janelle A.

2013-01-01

Purpose: To assess the hypothesis that the volume of whole brain that receives a certain dose level is primarily dependent on the treated volume rather than on the number, shape, or location of the lesions. This would help a physician validate the suitability of GammaKnife® based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for both oblong and spherical shaped lesions of various numbers and sizes. Forty patients who underwent GKSR [mean age of 54 years (range 7–80), mean number of lesions of 2.5 (range 1–6), and mean lesion volume of 4.4 cm3 (range 0.02–22.2 cm3)] were also studied retrospectively. Following recommendations of QUANTEC, the volume of brain irradiated by the 12 Gy (VB12) isodose line was measured and a power-law based relation is proposed here for estimating VB12 from the known tumor volume and the prescription dose. Results: In the simulation study on oblong, spherical, and multiple lesions, the volume of brain irradiated by 50%, 10%, and 1% of maximum dose was found to have linear, linear, and exponentially increasing dependence on the volume of the treated region, respectively. In the retrospective study on 40 GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9. In both the studies, the volume of brain irradiated by a certain dose level does not have a statistically significant relationship (p ≥ 0.05) with the number, shape, or position of the lesions. The measured VB12 agrees with calculation to within 1.7%. Conclusions: The results from the simulation and the retrospective clinical studies indicate that the volume of whole brain that receives a certain percentage of the maximum dose is primarily dependent on the treated volume and less on the number, shape, and location of the lesions. PMID:24007147

Dose-effect relationships, epidemiological analysis and the derivation of low dose risk.

PubMed

Leenhouts, H P; Chadwick, K H

2011-03-01

This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.

Modelling carcinogenesis after radiotherapy using Poisson statistics: implications for IMRT, protons and ions.

PubMed

Jones, Bleddyn

2009-06-01

Current technical radiotherapy advances aim to (a) better conform the dose contours to cancers and (b) reduce the integral dose exposure and thereby minimise unnecessary dose exposure to normal tissues unaffected by the cancer. Various types of conformal and intensity modulated radiotherapy (IMRT) using x-rays can achieve (a) while charged particle therapy (CPT)-using proton and ion beams-can achieve both (a) and (b), but at greater financial cost. Not only is the long term risk of radiation related normal tissue complications important, but so is the risk of carcinogenesis. Physical dose distribution plans can be generated to show the differences between the above techniques. IMRT is associated with a dose bath of low to medium dose due to fluence transfer: dose is effectively transferred from designated organs at risk to other areas; thus dose and risk are transferred. Many clinicians are concerned that there may be additional carcinogenesis many years after IMRT. CPT reduces the total energy deposition in the body and offers many potential advantages in terms of the prospects for better quality of life along with cancer cure. With C ions there is a tail of dose beyond the Bragg peaks, due to nuclear fragmentation; this is not found with protons. CPT generally uses higher linear energy transfer (which varies with particle and energy), which carries a higher relative risk of malignant induction, but also of cell death quantified by the relative biological effect concept, so at higher dose levels the frank development of malignancy should be reduced. Standard linear radioprotection models have been used to show a reduction in carcinogenesis risk of between two- and 15-fold depending on the CPT location. But the standard risk models make no allowance for fractionation and some have a dose limit at 4 Gy. Alternatively, tentative application of the linear quadratic model and Poissonian statistics to chromosome breakage and cell kill simultaneously allows estimation of relative changes in carcinogenesis that incorporate fractionation and relative biological effects (RBE). This alternative modelling approach allows absolute and relative risk estimations per cell and can be extended to tissues. The classical turnover point in carcinogenesis occurring after a single exposure is a feature of the model; also, the dose-response relationship becomes pseudo-linear with extended fractionation and when heterogeneity of the radiosensitivity parameters is introduced; there is also an inverse relationship between dose per fraction and cancer induction. In principle, this new approach might influence the conduct of proton and ion beam therapy, particularly beam placements and fractionation policies. The theoretical implications for future radiotherapy are considerable, but these predictions should be subjected to cellular and tissue experiments that simulate these forms of treatment, including any secondary neutron production in some cases depending on the beam delivery technique, e.g. in tissue equivalent humanoid phantoms using cell transformation techniques. Since the UK has no working high energy particle beam facility over 100 MeV, British scientists would require use of particle beam facilities in Europe, USA or Japan to perform experiments.

Source position verification and dosimetry in HDR brachytherapy using an EPID.

PubMed

Smith, R L; Taylor, M L; McDermott, L N; Haworth, A; Millar, J L; Franich, R D

2013-11-01

Accurate treatment delivery in high dose rate (HDR) brachytherapy requires correct source dwell positions and dwell times to be administered relative to each other and to the surrounding anatomy. Treatment delivery inaccuracies predominantly occur for two reasons: (i) anatomical movement or (ii) as a result of human errors that are usually related to incorrect implementation of the planned treatment. Electronic portal imaging devices (EPIDs) were originally developed for patient position verification in external beam radiotherapy and their application has been extended to provide dosimetric information. The authors have characterized the response of an EPID for use with an (192)Ir brachytherapy source to demonstrate its use as a verification device, providing both source position and dosimetric information. Characterization of the EPID response using an (192)Ir brachytherapy source included investigations of reproducibility, linearity with dose rate, photon energy dependence, and charge build-up effects associated with exposure time and image acquisition time. Source position resolution in three dimensions was determined. To illustrate treatment verification, a simple treatment plan was delivered to a phantom and the measured EPID dose distribution compared with the planned dose. The mean absolute source position error in the plane parallel to the EPID, for dwells measured at 50, 100, and 150 mm source to detector distances (SDD), was determined to be 0.26 mm. The resolution of the z coordinate (perpendicular distance from detector plane) is SDD dependent with 95% confidence intervals of ± 0.1, ± 0.5, and ± 2.0 mm at SDDs of 50, 100, and 150 mm, respectively. The response of the EPID is highly linear to dose rate. The EPID exhibits an over-response to low energy incident photons and this nonlinearity is incorporated into the dose calibration procedure. A distance (spectral) dependent dose rate calibration procedure has been developed. The difference between measured and planned dose is less than 2% for 98.0% of pixels in a two-dimensional plane at an SDD of 100 mm. Our application of EPID dosimetry to HDR brachytherapy provides a quality assurance measure of the geometrical distribution of the delivered dose as well as the source positions, which is not possible with any current HDR brachytherapy verification system.

TH-CD-201-03: A Real-Time Method to Simultaneously Measure Linear Energy Transfer and Dose for Proton Therapy Using Organic Scintillators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alsanea, F; Therriault-Proulx, F; Sawakuchi, G

Purpose: The light generated in organic scintillators depends on both the radiation dose and the linear energy transfer (LET). The LET dependence leads to an under-response of the detector in the Bragg peak of proton beams. This phenomenon, called ionization quenching, must be corrected to obtain accurate dose measurements of proton beams. This work exploits the ionization quenching phenomenon to provide a method of measuring LET and auto correcting quenching. Methods: We exposed simultaneously four different organic scintillators (BCF-12, PMMA, PVT, and LSD; 1mm in diameter) and a plane parallel ionization chamber in passively scattered proton beams to doses betweenmore » 32 and 43 cGy and fluence averaged LET values from 0.47 to 1.26 keV/µm. The LET values for each irradiation condition were determined using a validated Monte Carlo model of the beam line. We determined the quenching parameter in the Birk’s equation for scintillation in BCF-12 for dose measurements. One set of irradiation conditions was used to correlate the scintillation response ratio to the LET values and plot a scintillation response ratio versus LET calibration curve. Irradiation conditions independent from the calibration ones were used to validate this method. Comparisons to the expected values were made on both the basis of dose and LET. Results: Among all the scintillators investigated, the ratio of PMMA to BCF-12 provided the best correlation to LET values and was used as the LET calibration curve. The expected LET values in the validation set were within 2%±6%, which resulted in dose accuracy of 1.5%±5.8% for the range of LET values investigated in this work. Conclusion: We have demonstrated the feasibility of using the ratio between the light output of two organic scintillators to simultaneously measure LET and dose of therapeutic proton beams. Further studies are needed to verify the response in higher LET values.« less

Age-specific changes in the regulation of LH-dependent testosterone secretion: assessing responsiveness to varying endogenous gonadotropin output in normal men.

PubMed

Liu, Peter Y; Takahashi, Paul Y; Roebuck, Pamela D; Iranmanesh, Ali; Veldhuis, Johannes D

2005-09-01

Pulsatile and thus total testosterone (Te) secretion declines in older men, albeit for unknown reasons. Analytical models forecast that aging may reduce the capability of endogenous luteinizing hormone (LH) pulses to stimulate Leydig cell steroidogenesis. This notion has been difficult to test experimentally. The present study used graded doses of a selective gonadotropin releasing hormone (GnRH)-receptor antagonist to yield four distinct strata of pulsatile LH release in each of 18 healthy men ages 23-72 yr. Deconvolution analysis was applied to frequently sampled LH and Te concentration time series to quantitate pulsatile Te secretion over a 16-h interval. Log-linear regression was used to relate pulsatile LH secretion to attendant pulsatile Te secretion (LH-Te drive) across the four stepwise interventions in each subject. Linear regression of the 18 individual estimates of LH-Te feedforward dose-response slopes on age disclosed a strongly negative relationship (r = -0.721, P < 0.001). Accordingly, the present data support the thesis that aging in healthy men attenuates amplitude-dependent LH drive of burst-like Te secretion. The experimental strategy of graded suppression of neuroglandular outflow may have utility in estimating dose-response adaptations in other endocrine systems.

Out-of-field neutron and leakage photon exposures and the associated risk of second cancers in high-energy photon radiotherapy: current status.

PubMed

Takam, R; Bezak, E; Marcu, L G; Yeoh, E

2011-10-01

Determination and understanding of out-of-field neutron and photon doses in accelerator-based radiotherapy is an important issue since linear accelerators operating at high energies (>10 MV) produce secondary radiations that irradiate parts of the patient's anatomy distal to the target region, potentially resulting in detrimental health effects. This paper provides a compilation of data (technical and clinical) reported in the literature on the measurement and Monte Carlo simulations of peripheral neutron and photon doses produced from high-energy medical linear accelerators and the reported risk and/or incidence of second primary cancer of tissues distal to the target volume. Information in the tables facilitates easier identification of (1) the various methods and measurement techniques used to determine the out-of-field neutron and photon radiations, (2) reported linac-dependent out-of-field doses, and (3) the risk/incidence of second cancers after radiotherapy due to classic and modern treatment methods. Regardless of the measurement technique and type of accelerator, the neutron dose equivalent per unit photon dose ranges from as low as 0.1 mSv/Gy to as high as 20.4 mSv/Gy. This radiation dose potentially contributes to the induction of second primary cancer in normal tissues outside the treated area.

Assessment of selenium bioavailability from naturally produced high-selenium soy foods in selenium-deficient rats.

PubMed

Yan, Lin; Reeves, Philip G; Johnson, LuAnn K

2010-10-01

We assessed the bioavailability of selenium (Se) from a protein isolate and tofu (bean curd) prepared from naturally produced high-Se soybeans. The Se concentrations of the soybeans, the protein isolate and tofu were 5.2±0.2, 11.4±0.1 and 7.4±0.1mg/kg, respectively. Male weanling Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet (4.1μg Se/kg) for 56 days, and then they were replenished with Se for an additional 50 days by feeding them the same diet containing 14, 24 or 30 μg Se/kg from the protein isolate or 13, 23 or 31 μg Se/kg from tofu, respectively. l-Selenomethionine (SeMet) was used as a reference. Selenium bioavailability was determined on the basis of the restoration of Se-dependent enzyme activities and tissue Se concentrations in Se-depleted rats, comparing those responses for the protein isolate and tofu to those for SeMet by using a slope-ratio method. Dietary supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in glutathione peroxidase activities in blood and liver and in thioredoxin reductase activity in liver. Furthermore, supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in the Se concentrations of plasma, liver, muscle and kidneys. These results indicated an overall bioavailability of approximately 101% for Se from the protein isolate and 94% from tofu, relative to SeMet. We conclude that Se from naturally produced high-Se soybeans is highly bioavailable in this model and that high-Se soybeans may be a good dietary source of Se. Published by Elsevier GmbH.

Effect of radiation protraction on BED in the case of large fraction dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuperman, V. Y.

2013-08-15

Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the conditionmore » of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.« less

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

Dosimetry investigation of MOSFET for clinical IMRT dose verification.

PubMed

Deshpande, Sudesh; Kumar, Rajesh; Ghadi, Yogesh; Neharu, R M; Kannan, V

2013-06-01

In IMRT, patient-specific dose verification is followed regularly at each centre. Simple and efficient dosimetry techniques play a very important role in routine clinical dosimetry QA. The MOSFET dosimeter offers several advantages over the conventional dosimeters such as its small detector size, immediate readout, immediate reuse, multiple point dose measurements. To use the MOSFET as routine clinical dosimetry system for pre-treatment dose verification in IMRT, a comprehensive set of experiments has been conducted, to investigate its linearity, reproducibility, dose rate effect and angular dependence for 6 MV x-ray beam. The MOSFETs shows a linear response with linearity coefficient of 0.992 for a dose range of 35 cGy to 427 cGy. The reproducibility of the MOSFET was measured by irradiating the MOSFET for ten consecutive irradiations in the dose range of 35 cGy to 427 cGy. The measured reproducibility of MOSFET was found to be within 4% up to 70 cGy and within 1.4% above 70 cGy. The dose rate effect on the MOSFET was investigated in the dose rate range 100 MU/min to 600 MU/min. The response of the MOSFET varies from -1.7% to 2.1%. The angular responses of the MOSFETs were measured at 10 degrees intervals from 90 to 270 degrees in an anticlockwise direction and normalized at gantry angle zero and it was found to be in the range of 0.98 ± 0.014 to 1.01 ± 0.014. The MOSFETs were calibrated in a phantom which was later used for IMRT verification. The measured calibration coefficients were found to be 1 mV/cGy and 2.995 mV/cGy in standard and high sensitivity mode respectively. The MOSFETs were used for pre-treatment dose verification in IMRT. Nine dosimeters were used for each patient to measure the dose in different plane. The average variation between calculated and measured dose at any location was within 3%. Dose verification using MOSFET and IMRT phantom was found to quick and efficient and well suited for a busy radiotherapy department.

Development and evaluation of polycrystalline cadmium telluride dosimeters for accurate quality assurance in radiation therapy

NASA Astrophysics Data System (ADS)

Oh, K.; Han, M.; Kim, K.; Heo, Y.; Moon, C.; Park, S.; Nam, S.

2016-02-01

For quality assurance in radiation therapy, several types of dosimeters are used such as ionization chambers, radiographic films, thermo-luminescent dosimeter (TLD), and semiconductor dosimeters. Among them, semiconductor dosimeters are particularly useful for in vivo dosimeters or high dose gradient area such as the penumbra region because they are more sensitive and smaller in size compared to typical dosimeters. In this study, we developed and evaluated Cadmium Telluride (CdTe) dosimeters, one of the most promising semiconductor dosimeters due to their high quantum efficiency and charge collection efficiency. Such CdTe dosimeters include single crystal form and polycrystalline form depending upon the fabrication process. Both types of CdTe dosimeters are commercially available, but only the polycrystalline form is suitable for radiation dosimeters, since it is less affected by volumetric effect and energy dependence. To develop and evaluate polycrystalline CdTe dosimeters, polycrystalline CdTe films were prepared by thermal evaporation. After that, CdTeO3 layer, thin oxide layer, was deposited on top of the CdTe film by RF sputtering to improve charge carrier transport properties and to reduce leakage current. Also, the CdTeO3 layer which acts as a passivation layer help the dosimeter to reduce their sensitivity changes with repeated use due to radiation damage. Finally, the top and bottom electrodes, In/Ti and Pt, were used to have Schottky contact. Subsequently, the electrical properties under high energy photon beams from linear accelerator (LINAC), such as response coincidence, dose linearity, dose rate dependence, reproducibility, and percentage depth dose, were measured to evaluate polycrystalline CdTe dosimeters. In addition, we compared the experimental data of the dosimeter fabricated in this study with those of the silicon diode dosimeter and Thimble ionization chamber which widely used in routine dosimetry system and dose measurements for radiation therapy.

Dosimetric characterization of a microDiamond detector in clinical scanned carbon ion beams.

PubMed

Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G; Ciocca, M; Mirandola, A; Mairani, A; Raffaele, L; Magro, G

2015-04-01

To investigate for the first time the dosimetric properties of a new commercial synthetic diamond detector (PTW microDiamond) in high-energy scanned clinical carbon ion beams generated by a synchrotron at the CNAO facility. The detector response was evaluated in a water phantom with actively scanned carbon ion beams ranging from 115 to 380 MeV/u (30-250 mm Bragg peak depth in water). Homogeneous square fields of 3 × 3 and 6 × 6 cm(2) were used. Short- and medium-term (2 months) detector response stability, dependence on beam energy as well as ion type (carbon ions and protons), linearity with dose, and directional and dose-rate dependence were investigated. The depth dose curve of a 280 MeV/u carbon ion beam, scanned over a 3 × 3 cm(2) area, was measured with the microDiamond detector and compared to that measured using a PTW Advanced Markus ionization chamber, and also simulated using fluka Monte Carlo code. The detector response in two spread-out-Bragg-peaks (SOBPs), respectively, centered at 9 and 21 cm depths in water and calculated using the treatment planning system (TPS) used at CNAO, was measured. A negligible drift of detector sensitivity within the experimental session was seen, indicating that no detector preirradiation was needed. Short-term response reproducibility around 1% (1 standard deviation) was found. Only 2% maximum variation of microDiamond sensitivity was observed among all the evaluated proton and carbon ion beam energies. The detector response showed a good linear behavior. Detector sensitivity was found to be dose-rate independent, with a variation below 1.3% in the evaluated dose-rate range. A very good agreement between measured and simulated Bragg curves with both microDiamond and Advanced Markus chamber was found, showing a negligible LET dependence of the tested detector. A depth dose curve was also measured by positioning the microDiamond with its main axis oriented orthogonally to the beam direction. A strong distortion in Bragg peak measurement was observed, confirming manufacturer recommendation on avoiding such configuration. Very good results were obtained for SOBP measurements, with a difference below 1% between measured and TPS-calculated doses. The stability of detector sensitivity in the observation period was within the experimental uncertainty. Dosimetric characterization of a PTW microDiamond detector in high-energy scanned carbon ion beams was performed. The results of the present study showed that this detector is suitable for dosimetry of clinical carbon ion beams, with a negligible LET and dose-rate dependence.

A new single crystal diamond dosimeter for small beam: comparison with different commercial active detectors.

PubMed

Marsolat, F; Tromson, D; Tranchant, N; Pomorski, M; Le Roy, M; Donois, M; Moignau, F; Ostrowsky, A; De Carlan, L; Bassinet, C; Huet, C; Derreumaux, S; Chea, M; Cristina, K; Boisserie, G; Bergonzo, P

2013-11-07

Recent developments of new therapy techniques using small photon beams, such as stereotactic radiotherapy, require suitable detectors to determine the delivered dose with a high accuracy. The dosimeter has to be as close as possible to tissue equivalence and to exhibit a small detection volume compared to the size of the irradiation field, because of the lack of lateral electronic equilibrium in small beam. Characteristics of single crystal diamond (tissue equivalent material Z = 6, high density) make it an ideal candidate to fulfil most of small beam dosimetry requirements. A commercially available Element Six electronic grade synthetic diamond was used to develop a single crystal diamond dosimeter (SCDDo) with a small detection volume (0.165 mm(3)). Long term stability was studied by irradiating the SCDDo in a (60)Co beam over 14 h. A good stability (deviation less than ± 0.1%) was observed. Repeatability, dose linearity, dose rate dependence and energy dependence were studied in a 10 × 10 cm(2) beam produced by a Varian Clinac 2100 C linear accelerator. SCDDo lateral dose profile, depth dose curve and output factor (OF) measurements were performed for small photon beams with a micro multileaf collimator m3 (BrainLab) attached to the linac. This study is focused on the comparison of SCDDo measurements to those obtained with different commercially available active detectors: an unshielded silicon diode (PTW 60017), a shielded silicon diode (Sun Nuclear EDGE), a PinPoint ionization chamber (PTW 31014) and two natural diamond detectors (PTW 60003). SCDDo presents an excellent spatial resolution for dose profile measurements, due to its small detection volume. Low energy dependence (variation of 1.2% between 6 and 18 MV photon beam) and low dose rate dependence of the SCDDo (variation of 1% between 0.53 and 2.64 Gy min(-1)) are obtained, explaining the good agreement between the SCDDo and the efficient unshielded diode (PTW 60017) in depth dose curve measurements. For field sizes ranging from 0.6 × 0.6 to 10 × 10 cm(2), OFs obtained with the SCDDo are between the OFs measured with the PinPoint ionization chamber and the Sun Nuclear EDGE diode that are known to respectively underestimate and overestimate OF values in small beam, due to the large detection volume of the chamber and the non-water equivalence of both detectors.

How feasible is remote 3D dosimetry for MR guided Radiation Therapy (MRgRT)?

NASA Astrophysics Data System (ADS)

Mein, S.; Rankine, L.; Miles, D.; Juang, T.; Cai, B.; Curcuru, A.; Mutic, S.; Fenoli, J.; Adamovics, J.; Li, H.; Oldham, M.

2017-05-01

To develop and apply a remote dosimetry protocol with PRESAGE® radiochromic plastic and optical-CT readout in the validation of MRI guided radiation therapy (MRgRT) treatments (MRIdian® by ViewRay®). Through multi-institutional collaboration we performed PRESAGE® dosimetry studies in 4ml cuvettes to investigate dose-response linearity, MR-compatibility, and energy-independence. An open calibration field and symmetrical 3-field plans were delivered to 10cm diameter PRESAGE® to examine percent depth dose and response uniformity under a magnetic field. Evidence of non-linear dose response led to a large volume PRESAGE® study where small corrections were developed for temporally- and spatially-dependent behaviors observed between irradiation and delayed readout. TG-119 plans were created in the MRIdian® TPS and then delivered to 14.5cm 2kg PRESAGE® dosimeters. Through the domestic investigation of an off-site MRgRT system, a refined 3D remote dosimetry protocol is presented capable of validation of advanced MRgRT radiation treatments.

Determining the applicability of the Landauer nanoDot as a general public dosimeter in a research imaging facility.

PubMed

Charlton, Michael A; Thoreson, Kelly F; Cerecero, Jennifer A

2012-11-01

The Research Imaging Institute (RII) building at the University of Texas Health Science Center at San Antonio (UTHSCSA) houses two cyclotron particle accelerators, positron emission tomography (PET) machines, and a fluoroscopic unit. As part of the radiation protection program (RPP) and meeting the standard for achieving ALARA (as low as reasonably achievable), it is essential to minimize the ionizing radiation exposure to the general public through the use of controlled areas and area dose monitoring. Currently, thirty-four whole body Luxel+ dosimeters, manufactured by Landauer, are being used in various locations within the RII to monitor dose to the general public. The intent of this research was to determine if the nanoDot, a single point dosimeter, can be used as a general public dosimeter in a diagnostic facility. This was tested by first verifying characteristics of the nanoDot dosimeter including dose linearity, dose rate dependence, angular dependence, and energy dependence. Then, the response of the nanoDot dosimeter to the Luxel+ dosimeter when placed in a continuous, low dose environment was investigated. Finally, the nanoDot was checked for appropriate response in an acute, high dose environment. Based on the results, the current recommendation is that the nanoDot should not replace the Luxel+ dosimeter without further work to determine the energy spectra in the RII building and without considering the limitation of the microStar reader, portable on-site OSL reader, at doses below 0.1 mGy (10 mrad).

Near infrared radio-luminescence of O{sub 2} loaded radiation hardened silica optical fibers: A candidate dosimeter for harsh environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Francesca, D., E-mail: diego.di.francesca@univ-st-etienne.fr; Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, I-90123 Palermo; Girard, S.

2014-11-03

We report on an experimental investigation of the infrared Radio-Luminescence (iRL) emission of interstitial O{sub 2} molecules loaded in radiation hardened pure-silica-core and fluorine-doped silica-based optical fibers (OFs). The O{sub 2} loading treatment successfully dissolved high concentrations of oxygen molecules into the silica matrix. A sharp luminescence at 1272 nm was detected when 2.5 cm of the treated OFs were irradiated with 10 keV X-rays. This emission originates from the radiative decay of the first excited singlet state of the embedded O{sub 2} molecules. The dose, dose-rate, and temperature dependencies of the infrared emission are studied through in situ optical measurements. The resultsmore » show that the iRL is quite stable in doses of up to 1 MGy(SiO{sub 2}) and is linearly dependent on the dose-rate up to the maximum investigated dose-rate of ∼200 kGy(SiO{sub 2})/h. The temperature dependency of the iRL shows a decrease in efficiency above 200 °C, which is attributed to the non-radiative decay of the excited O{sub 2} molecules. The results obtained and the long-term stability of the O{sub 2}-loading treatment (no out-gassing effect) strongly suggest the applicability of these components to real-time remote dosimetry in environments characterized by high radiation doses and dose-rates.« less

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 03: Energy dependence of a clinical probe-format calorimeter and its pertinence to absolute photon and electron beam dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, James; Seuntjens, Jan; Sarfehnia, Arman

Purpose: To evaluate the intrinsic and absorbed-dose energy dependence of a small-scale graphite calorimeter probe (GPC) developed for use as a routine clinical dosimeter. The influence of charge deposition on the response of the GPC was also assessed by performing absolute dosimetry in clinical linac-based electron beams. Methods: Intrinsic energy dependence was determined by performing constant-temperature calorimetry dose measurements in a water-equivalent solid phantom, under otherwise reference conditions, in five high-energy photon (63.5 < %dd(10){sub X} < 76.3), and five electron (2.3 cm < R{sub 50} < 8.3 cm) beams. Reference dosimetry was performed for all beams in question usingmore » an Exradin A19 ion chamber with a calibration traceable to national standards. The absorbed-dose component of the overall energy dependence was calculated using the EGSnrc egs-chamber user code. Results: A total of 72 measurements were performed with the GPC, resulting in a standard error on the mean absorbed dose of better than 0.3 % for all ten beams. For both the photon and electron beams, no statistically-significant energy dependence was observed experimentally. Peak-to-peak, variations in the relative response of the GPC across all beam qualities of a given radiation type were on the order of 1 %. No effects, either transient or permanent, were attributable to the charge deposited by the electron beams. Conclusions: The GPC’s apparent energy-independence, combined with its well-established linearity and dose rate independence, make it a potentially useful dosimetry system capable measuring photon and electron doses in absolute terms at the clinical level.« less

SU-C-16A-02: A Beryllium Oxide (BeO) Fibre-Coupled Luminescence Dosimeter for High Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santos, A; Institute for Photonics and Advanced Sensing and School of Chem and Phys, Adelaide, South Australia; Mohammadi, M

Purpose: Beryllium oxide (BeO) ceramics have an effective atomic number, zeff ∼7.1, closely matched to water, zeff ∼7.4. The purpose of this study was to evaluate the use of a beryllium oxide (BeO) ceramic fibrecoupled luminescence dosimeter, named RL/OSL BeO FOD, for high dose rate (HDR) brachytherapy dosimetry. In our dosimetry system the radioluminescence (RL) of BeO ceramics is utilized for dose-rate measurements, and the optically stimulated luminescence (OSL) can be read post exposure for accumulated dose measurements. Methods: The RL/OSL BeO FOD consists of a 1 mm diameter × 1 mm long cylinder of BeO ceramic coupled to amore » 15 m long silica-silica optical fibre. The optical fibre is connected to a custom developed portable RL and OSL reader, located outside of the treatment suite. The x-ray energy response was evaluated using superficial x-rays, an Ir-192 source and high energy linear accelerators. The RL/OSL BeO FOD was then characterised for an Ir-192 source, investigating the dose response and angular dependency. A depth dose curve for the Ir-192 source was also measured. Results: The RL/OSL BeO FOD shows an under-response at low energy x-rays as expected. Though at higher x-ray energies, the OSL response continued to increase, while the RL response remained relatively constant. The dose response for the RL is found to be linear up to doses of 15 Gy, while the OSL response becomes more supralinear to doses above 15 Gy. Little angular dependency is observed and the depth dose curve measured agreed within 4% of that calculated based on TG-43. Conclusion: This works shows that the RL/OSL BeO FOD can be useful in HDR dosimetry. With the RL/OSL BeO FODs current size, it is capable of being inserted into intraluminal catheters and interstitial needles to verify HDR treatments.« less

Development of a stable and sensitive semiconductor detector by using a mixture of lead(II) iodide and lead monoxide for NDT radiation dose detection

NASA Astrophysics Data System (ADS)

Heo, Y. J.; Kim, K. T.; Han, M. J.; Moon, C. W.; Kim, J. E.; Park, J. K.; Park, S. K.

2018-03-01

Recently, high-energy radiation has been widely used in various industrial fields, including the medical industry, and increasing research efforts have been devoted to the development of radiation detectors to be used with high-energy radiation. In particular, nondestructive industrial applications use high-energy radiation for ships and multilayered objects for accurate inspection. Therefore, it is crucial to verify the accuracy of radiation dose measurements and evaluate the precision and reproducibility of the radiation output dose. Representative detectors currently used for detecting the dose in high-energy regions include Si diodes, diamond diodes, and ionization chambers. However, the process of preparing these detectors is complex in addition to the processes of conducting dosimetric measurements, analysis, and evaluation. Furthermore, the minimum size that can be prepared for a detector is limited. In the present study, the disadvantages of original detectors are compensated by the development of a detector made of a mixture of polycrystalline PbI2 and PbO powder, which are both excellent semiconducting materials suitable for detecting high-energy gamma rays and X-rays. The proposed detector shows characteristics of excellent reproducibility and stable signal detection in response to the changes in energy, and was analyzed for its applicability. Moreover, the detector was prepared through a simple process of particle-in-binder to gain control over the thickness and meet the specific value designated by the user. A mixture mass ratio with the highest reproducibility was determined through reproducibility testing with respect to changes in the photon energy. The proposed detector was evaluated for its detection response characteristics with respect to high-energy photon beam, in terms of dose-rate dependence, sensitivity, and linearity evaluation. In the reproducibility assessment, the detector made with 15 wt% PbO powder showed the best characteristics of 0.59% and 0.25% at 6 and 15 MV, respectively. Based on its selection in the reproducibility assessment, the 15 wt% PbO detector showed no dependence on the dose-rate changes, with R-SD < 1%. Finally, a coefficient of determination of 1 in the linearity assessment demonstrated very good linearity with regards to changes in dose. These results demonstrate the applicability and usefulness of the proposed detector made from a mixture of PbI2 and PbO semiconductors.

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

NASA Astrophysics Data System (ADS)

Morén, B.; Larsson, T.; Carlsson Tedgren, Å.

2018-03-01

High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Safety and pharmacokinetics of the oral iron chelator SP-420 in β-thalassemia.

PubMed

Taher, Ali T; Saliba, Antoine N; Kuo, Kevin H; Giardina, Patricia J; Cohen, Alan R; Neufeld, Ellis J; Aydinok, Yesim; Kwiatkowski, Janet L; Jeglinski, Brenda I; Pietropaolo, Keith; Berk, Gregory; Viprakasit, Vip

2017-12-01

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for C max and AUC 0-τ over the dose range evaluated. The median t max ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug. © 2017 Wiley Periodicals, Inc.

Beam energy considerations for gold nano-particle enhanced radiation treatment.

PubMed

Van den Heuvel, F; Locquet, Jean-Pierre; Nuyts, S

2010-08-21

A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.

Beam energy considerations for gold nano-particle enhanced radiation treatment

NASA Astrophysics Data System (ADS)

Van den Heuvel, F.; Locquet, Jean-Pierre; Nuyts, S.

2010-08-01

A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.

Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP

PubMed Central

Kusuhara, Hiroyuki; Furuie, Hidetoshi; Inano, Akihiro; Sunagawa, Akihiro; Yamada, Saiko; Wu, Chunyong; Fukizawa, Shinya; Morimoto, Nozomi; Ieiri, Ichiro; Morishita, Mariko; Sumita, Kiminobu; Mayahara, Hiroshi; Fujita, Takuya; Maeda, Kazuya; Sugiyama, Yuichi

2012-01-01

BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP-dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild-type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1. KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild-type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0-fold at microdoses and 3.2-fold at therapeutic doses in humans. Non-linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1. CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose–exposure relationship of sulphasalazine. PMID:22300367

Energy dependence corrections to MOSFET dosimetric sensitivity.

PubMed

Cheung, T; Butson, M J; Yu, P K N

2009-03-01

Metal Oxide Semiconductor Field Effect Transistors (MOSFET's) are dosimeters which are now frequently utilized in radiotherapy treatment applications. An improved MOSFET, clinical semiconductor dosimetry system (CSDS) which utilizes improved packaging for the MOSFET device has been studied for energy dependence of sensitivity to x-ray radiation measurement. Energy dependence from 50 kVp to 10 MV x-rays has been studied and found to vary by up to a factor of 3.2 with 75 kVp producing the highest sensitivity response. The detectors average life span in high sensitivity mode is energy related and ranges from approximately 100 Gy for 75 kVp x-rays to approximately 300 Gy at 6 MV x-ray energy. The MOSFET detector has also been studied for sensitivity variations with integrated dose history. It was found to become less sensitive to radiation with age and the magnitude of this effect is dependant on radiation energy with lower energies producing a larger sensitivity reduction with integrated dose. The reduction in sensitivity is however approximated reproducibly by a slightly non linear, second order polynomial function allowing corrections to be made to readings to account for this effect to provide more accurate dose assessments both in phantom and in-vivo.

Characterization of a synthetic single crystal diamond Schottky diode for radiotherapy electron beam dosimetry.

PubMed

Di Venanzio, C; Marinelli, Marco; Milani, E; Prestopino, G; Verona, C; Verona-Rinati, G; Falco, M D; Bagalà, P; Santoni, R; Pimpinella, M

2013-02-01

To investigate the dosimetric properties of synthetic single crystal diamond based Schottky diodes under irradiation with therapeutic electron beams from linear accelerators. A single crystal diamond detector was fabricated and tested under 6, 8, 10, 12, and 15 MeV electron beams. The detector performances were evaluated using three types of commercial detectors as reference dosimeters: an Advanced Markus plane parallel ionization chamber, a Semiflex cylindrical ionization chamber, and a p-type silicon detector. Preirradiation, linearity with dose, dose rate dependence, output factors, lateral field profiles, and percentage depth dose profiles were investigated and discussed. During preirradiation the diamond detector signal shows a weak decrease within 0.7% with respect to the plateau value and a final signal stability of 0.1% (1σ) is observed after about 5 Gy. A good linear behavior of the detector response as a function of the delivered dose is observed with deviations below ±0.3% in the dose range from 0.02 to 10 Gy. In addition, the detector response is dose rate independent, with deviations below 0.3% in the investigated dose rate range from 0.17 to 5.45 Gy∕min. Percentage depth dose curves obtained from the diamond detector are in good agreement with the ones from the reference dosimeters. Lateral beam profile measurements show an overall good agreement among detectors, taking into account their respective geometrical features. The spatial resolution of solid state detectors is confirmed to be better than that of ionization chambers, being the one from the diamond detector comparable to that of the silicon diode. A good agreement within experimental uncertainties was also found in terms of output factor measurements between the diamond detector and reference dosimeters. The observed dosimetric properties indicate that the tested diamond detector is a suitable candidate for clinical electron beam dosimetry.

Dosimetric evaluation of a new OneDose MOSFET for Ir-192 energy.

PubMed

Kinhikar, Rajesh A; Sharma, Pramod K; Tambe, Chandrashekhar M; Deshpande, Deepak D

2006-03-07

The purpose of this study was to investigate dosimetry (reproducibility, energy correction, relative response with distance from source, linearity with threshold dose, rate of fading, temperature and angular dependence) of a newly designed OneDosetrade mark MOSFET patient dosimetry system for use in HDR brachytherapy with Ir-192 energy. All measurements were performed with a MicroSelectron HDR unit and OneDose MOSFET detectors. All dosimeters were normalized to 3 min post-irradiation to minimize fading effects. All dosimeters gave reproducible readings with mean deviation of 1.8% (SD 0.4) and 2.4% (SD 0.6) for 0 degrees and 180 degrees incidences, respectively. The mean energy correction factor was found to be 1.1 (range 1.06-1.12). Overall, there was 60% and 40% mean response of the MOSFET at 2 and 3 cm, respectively, from the source. MOSFET results showed good agreement with TLD and parallel plate ion chamber. Linear dose response with threshold voltage shift was observed with applied doses of 0.3 Gy-5 Gy with Ir-192 energy. Linearity (R2 = 1) was observed in the MOSFET signal with the applied dose range of 0.3 Gy-5 Gy with Ir-192 energy. Fading effects were less than 1% after 10 min and the MOSFET detectors stayed stable (within 5%) over a period of 1 month. The MOSFET response was found to be decreased by approximately 1.5% at 37 degrees C compared to 20 degrees C. The isotropic response of the MOSFET was found to be within +/-6%. A maximum deviation of 5.5% was obtained between 0 degrees and 180 degrees for both the axes and this should be considered in clinical applications. The small size, cable-less, instant readout, permanent storage of dose and ease of use make the MOSFET a novel dosimeter and beneficial to patients for skin dose measurements with HDRBT using an Ir-192 source compared to the labour demanding and time-consuming TLDs.

A multiscale filter for noise reduction of low-dose cone beam projections.

PubMed

Yao, Weiguang; Farr, Jonathan B

2015-08-21

The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, exp(-x2/2σ(2)(f)) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of σ(f), which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ(2)(f)) is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

Characterization of OSL dosimeters for use in dose assessment in Computed Tomography procedures.

PubMed

Giansante, Louise; Santos, Josilene C; Umisedo, Nancy K; Terini, Ricardo A; Costa, Paulo R

2018-03-01

This study describes the characterization of an Al 2 O 3 :C OSLD (Landauer's Luxel™ tape) for dose evaluation in Computed Tomography. The irradiations were conducted using both a constant potential X-ray equipment and a 64-slice clinical CT scanner, and the readouts were performed using a Risø TL/OSL reader. The following aspects were studied: batch homogeneity, energy response, linearity of dose response, reproducibility, reusability, and effect of uncertainties with the normalization of OSL signals per their response to beta radiation. A group of 330 dosimeters from the 452 irradiated with the same dose presented OSL signals within the interval of 4.7% from the average. The dosimeters presented energy-dependent response in good agreement with results found in the literature. The air kerma response of the OSL signal showed a linear trend for both the constant potential X-ray device and the clinical CT scanner, with differences in their slopes of approximately 10%. Reproducibility, reusability, and effect of beta normalization were analyzed by separating 72 dosimeters in 3 groups. The results obtained in this study together with those of previous works indicate that this type of dosimeter is adequate for dose evaluation in CT clinical applications. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

On the suitability of ultrathin detectors for absorbed dose assessment in the presence of high-density heterogeneities.

PubMed

Bueno, M; Carrasco, P; Jornet, N; Muñoz-Montplet, C; Duch, M A

2014-08-01

The aim of this study was to evaluate the suitability of several detectors for the determination of absorbed dose in bone. Three types of ultrathin LiF-based thermoluminescent dosimeters (TLDs)-two LiF:Mg,Cu,P-based (MCP-Ns and TLD-2000F) and a (7)Li-enriched LiF:Mg,Ti-based (MTS-7s)-as well as EBT2 Gafchromic films were used to measure percentage depth-dose distributions (PDDs) in a water-equivalent phantom with a bone-equivalent heterogeneity for 6 and 18 MV and a set of field sizes ranging from 5 x 5 cm2 to 20 x 20 cm2. MCP-Ns, TLD-2000F, MTS-7s, and EBT2 have active layers of 50, 20, 50, and 30 μm, respectively. Monte Carlo (MC) dose calculations (PENELOPE code) were used as the reference and helped to understand the experimental results and to evaluate the potential perturbation of the fluence in bone caused by the presence of the detectors. The energy dependence and linearity of the TLDs' response was evaluated. TLDs exhibited flat energy responses (within 2.5%) and linearity with dose (within 1.1%) within the range of interest for the selected beams. The results revealed that all considered detectors perturb the electron fluence with respect to the energy inside the bone-equivalent material. MCP-Ns and MTS-7s underestimated the absorbed dose in bone by 4%-5%. EBT2 exhibited comparable accuracy to MTS-7s and MCP-Ns. TLD-2000F was able to determine the dose within 2% accuracy. No dependence on the beam energy or field size was observed. The MC calculations showed that a[Formula: see text] thick detector can provide reliable dose estimations in bone regardless of whether it is made of LiF, water or EBT's active layer material. TLD-2000F was found to be suitable for providing reliable absorbed dose measurements in the presence of bone for high-energy x-ray beams.

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patwe, P; Mhatre, V; Dandekar, P

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation.

PubMed

Ding, Junjie; Wang, Yi; Lin, Weiwei; Wang, Changlian; Zhao, Limei; Li, Xingang; Zhao, Zhigang; Miao, Liyan; Jiao, Zheng

2015-03-01

Valproic acid (VPA) follows a non-linear pharmacokinetic profile in terms of protein-binding saturation. The total daily dose regarding VPA clearance is a simple power function, which may partially explain the non-linearity of the pharmacokinetic profile; however, it may be confounded by the therapeutic drug monitoring effect. The aim of this study was to develop a population pharmacokinetic model for VPA based on protein-binding saturation in pediatric patients with epilepsy. A total of 1,107 VPA serum trough concentrations at steady state were collected from 902 epileptic pediatric patients aged from 3 weeks to 14 years at three hospitals. The population pharmacokinetic model was developed using NONMEM(®) software. The ability of three candidate models (the simple power exponent model, the dose-dependent maximum effect [DDE] model, and the protein-binding model) to describe the non-linear pharmacokinetic profile of VPA was investigated, and potential covariates were screened using a stepwise approach. Bootstrap, normalized prediction distribution errors and external evaluations from two independent studies were performed to determine the stability and predictive performance of the candidate models. The age-dependent exponent model described the effects of body weight and age on the clearance well. Co-medication with carbamazepine was identified as a significant covariate. The DDE model best fitted the aim of this study, although there were no obvious differences in the predictive performances. The condition number was less than 500, and the precision of the parameter estimates was less than 30 %, indicating stability and validity of the final model. The DDE model successfully described the non-linear pharmacokinetics of VPA. Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations.

Total Dose Effects on Bipolar Integrated Circuits at Low Temperature

NASA Technical Reports Server (NTRS)

Johnston, A. H.; Swimm, R. T.; Thorbourn, D. O.

2012-01-01

Total dose damage in bipolar integrated circuits is investigated at low temperature, along with the temperature dependence of the electrical parameters of internal transistors. Bandgap narrowing causes the gain of npn transistors to decrease far more at low temperature compared to pnp transistors, due to the large difference in emitter doping concentration. When irradiations are done at temperatures of -140 deg C, no damage occurs until devices are warmed to temperatures above -50 deg C. After warm-up, subsequent cooling shows that damage is then present at low temperature. This can be explained by the very strong temperature dependence of dispersive transport in the continuous-time-random-walk model for hole transport. For linear integrated circuits, low temperature operation is affected by the strong temperature dependence of npn transistors along with the higher sensitivity of lateral and substrate pnp transistors to radiation damage.

Characterization of MOSkin detector for in vivo skin dose measurement during megavoltage radiotherapy

PubMed Central

Jong, Wei Loong; Wong, Jeannie Hsiu Ding; Ng, Kwan Hoong; Ho, Gwo Fuang; Cutajar, Dean L.; Rosenfeld, Anatoly B.

2014-01-01

In vivo dosimetry is important during radiotherapy to ensure the accuracy of the dose delivered to the treatment volume. A dosimeter should be characterized based on its application before it is used for in vivo dosimetry. In this study, we characterize a new MOSFET‐based detector, the MOSkin detector, on surface for in vivo skin dosimetry. The advantages of the MOSkin detector are its water equivalent depth of measurement of 0.07 mm, small physical size with submicron dosimetric volume, and the ability to provide real‐time readout. A MOSkin detector was calibrated and the reproducibility, linearity, and response over a large dose range to different threshold voltages were determined. Surface dose on solid water phantom was measured using MOSkin detector and compared with Markus ionization chamber and GAFCHROMIC EBT2 film measurements. Dependence in the response of the MOSkin detector on the surface of solid water phantom was also tested for different (i) source to surface distances (SSDs); (ii) field sizes; (iii) surface dose; (iv) radiation incident angles; and (v) wedges. The MOSkin detector showed excellent reproducibility and linearity for dose range of 50 cGy to 300 cGy. The MOSkin detector showed reliable response to different SSDs, field sizes, surface, radiation incident angles, and wedges. The MOSkin detector is suitable for in vivo skin dosimetry. PACS number: 87.55.Qr PMID:25207573

Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells

PubMed Central

Neumaier, Teresa; Swenson, Joel; Pham, Christopher; Polyzos, Aris; Lo, Alvin T.; Yang, PoAn; Dyball, Jane; Asaithamby, Aroumougame; Chen, David J.; Bissell, Mina J.; Thalhammer, Stefan; Costes, Sylvain V.

2012-01-01

The concept of DNA “repair centers” and the meaning of radiation-induced foci (RIF) in human cells have remained controversial. RIFs are characterized by the local recruitment of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we provide strong evidence for the existence of repair centers. We used live imaging and mathematical fitting of RIF kinetics to show that RIF induction rate increases with increasing radiation dose, whereas the rate at which RIFs disappear decreases. We show that multiple DNA double-strand breaks (DSBs) 1 to 2 μm apart can rapidly cluster into repair centers. Correcting mathematically for the dose dependence of induction/resolution rates, we observe an absolute RIF yield that is surprisingly much smaller at higher doses: 15 RIF/Gy after 2 Gy exposure compared to approximately 64 RIF/Gy after 0.1 Gy. Cumulative RIF counts from time lapse of 53BP1-GFP in human breast cells confirmed these results. The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation. PMID:22184222

Small field depth dose profile of 6 MV photon beam in a simple air-water heterogeneity combination: A comparison between anisotropic analytical algorithm dose estimation with thermoluminescent dosimeter dose measurement.

PubMed

Mandal, Abhijit; Ram, Chhape; Mourya, Ankur; Singh, Navin

2017-01-01

To establish trends of estimation error of dose calculation by anisotropic analytical algorithm (AAA) with respect to dose measured by thermoluminescent dosimeters (TLDs) in air-water heterogeneity for small field size photon. TLDs were irradiated along the central axis of the photon beam in four different solid water phantom geometries using three small field size single beams. The depth dose profiles were estimated using AAA calculation model for each field sizes. The estimated and measured depth dose profiles were compared. The over estimation (OE) within air cavity were dependent on field size (f) and distance (x) from solid water-air interface and formulated as OE = - (0.63 f + 9.40) x2+ (-2.73 f + 58.11) x + (0.06 f2 - 1.42 f + 15.67). In postcavity adjacent point and distal points from the interface have dependence on field size (f) and equations are OE = 0.42 f2 - 8.17 f + 71.63, OE = 0.84 f2 - 1.56 f + 17.57, respectively. The trend of estimation error of AAA dose calculation algorithm with respect to measured value have been formulated throughout the radiation path length along the central axis of 6 MV photon beam in air-water heterogeneity combination for small field size photon beam generated from a 6 MV linear accelerator.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar

Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex formore » each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.« less

Implementation of Size-Dependent Local Diagnostic Reference Levels for CT Angiography.

PubMed

Boere, Hub; Eijsvoogel, Nienke G; Sailer, Anna M; Wildberger, Joachim E; de Haan, Michiel W; Das, Marco; Jeukens, Cecile R L P N

2018-05-01

Diagnostic reference levels (DRLs) are established for standard-sized patients; however, patient dose in CT depends on patient size. The purpose of this study was to introduce a method for setting size-dependent local diagnostic reference levels (LDRLs) and to evaluate these LDRLs in comparison with size-independent LDRLs and with respect to image quality. One hundred eighty-four aortic CT angiography (CTA) examinations performed on either a second-generation or third-generation dual-source CT scanner were included; we refer to the second-generation dual-source CT scanner as "CT1" and the third-generation dual-source CT scanner as "CT2." The volume CT dose index (CTDI vol ) and patient diameter (i.e., the water-equivalent diameter) were retrieved by dose-monitoring software. Size-dependent DRLs based on a linear regression of the CTDI vol versus patient size were set by scanner type. Size-independent DRLs were set by the 5th and 95th percentiles of the CTDI vol values. Objective image quality was assessed using the signal-to-noise ratio (SNR), and subjective image quality was assessed using a 4-point Likert scale. The CTDI vol depended on patient size and scanner type (R 2 = 0.72 and 0.78, respectively; slope = 0.05 and 0.02 mGy/mm; p < 0.001). Of the outliers identified by size-independent DRLs, 30% (CT1) and 67% (CT2) were adequately dosed when considering patient size. Alternatively, 30% (CT1) and 70% (CT2) of the outliers found with size-dependent DRLs were not identified using size-independent DRLs. A negative correlation was found between SNR and CTDI vol (R 2 = 0.36 for CT1 and 0.45 for CT2). However, all outliers had a subjective image quality score of sufficient or better. We introduce a method for setting size-dependent LDRLs in CTA. Size-dependent LDRLs are relevant for assessing the appropriateness of the radiation dose for an individual patient on a specific CT scanner.

Measurement of neutron spectra generated from bombardment of 4 to 24 MeV protons on a thick ⁹Be target and estimation of neutron yields.

PubMed

Paul, Sabyasachi; Sahoo, G S; Tripathy, S P; Sharma, S C; Ramjilal; Ninawe, N G; Sunil, C; Gupta, A K; Bandyopadhyay, T

2014-06-01

A systematic study on the measurement of neutron spectra emitted from the interaction of protons of various energies with a thick beryllium target has been carried out. The measurements were carried out in the forward direction (at 0° with respect to the direction of protons) using CR-39 detectors. The doses were estimated using the in-house image analyzing program autoTRAK_n, which works on the principle of luminosity variation in and around the track boundaries. A total of six different proton energies starting from 4 MeV to 24 MeV with an energy gap of 4 MeV were chosen for the study of the neutron yields and the estimation of doses. Nearly, 92% of the recoil tracks developed after chemical etching were circular in nature, but the size distributions of the recoil tracks were not found to be linearly dependent on the projectile energy. The neutron yield and dose values were found to be increasing linearly with increasing projectile energies. The response of CR-39 detector was also investigated at different beam currents at two different proton energies. A linear increase of neutron yield with beam current was observed.

Radiation and breast cancer: a review of current evidence

PubMed Central

Ronckers, Cécile M; Erdmann, Christine A; Land, Charles E

2005-01-01

This paper summarizes current knowledge on ionizing radiation-associated breast cancer in the context of established breast cancer risk factors, the radiation dose–response relationship, and modifiers of dose response, taking into account epidemiological studies and animal experiments. Available epidemiological data support a linear dose–response relationship down to doses as low as about 100 mSv. However, the magnitude of risk per unit dose depends strongly on when radiation exposure occurs: exposure before the age of 20 years carries the greatest risk. Other characteristics that may influence the magnitude of dose-specific risk include attained age (that is, age at observation for risk), age at first full-term birth, parity, and possibly a history of benign breast disease, exposure to radiation while pregnant, and genetic factors. PMID:15642178

Induction of sister chromatid exchanges and inhibition of cellular proliferation in vitro. I. Caffeine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guglielmi, G.E.; Vogt, T.F.; Tice, R.R.

1982-01-01

While many agents have been examined for their ability to induce SCE's, complete dose-response information has often been lacking. We have reexamined the ability of one such compound - caffeine - to induce SCEs and also to inhibit cellular proliferation in human peripheral lymphocytes in vitro. An acute exposure to caffeine prior to the DNA synthetic period did not affect either SCE frequency or the rate of cellular proliferation. Chronic exposure to caffeine throughout the culture period lead to both a dose-dependent increase in SCEs (SCE/sub d/ or doubling dose = 2.4 mM; SCE/sub 10/ or the dose capable ofmore » inducing 10 SCE = 1.4 mM) and a dose-dependent inhibition of cellular proliferation (IC/sub 50/ or the 50% inhibition concentration = 2.6 mM). The relative proportion of first generation metaphase cells, an assessment of proliferative inhibiton, increased linearly with increasing caffeine concentrations. However, SCE frequency increased nonlinearly over the same range of caffeine concentrations. Examination of the ratio of nonsymmetrical to symmetrical SCEs in third generation metaphase cells indicated that caffeine induced SCEs in equal frequency in each of three successive generations. The dependency of SCE induction and cellular proliferative inhibition on caffeine's presence during the DNA synthetic period suggests that caffeine may act as an antimetabolite in normal human cells.« less

Development and clinical evaluation of an ionization chamber array with 3.5 mm pixel pitch for quality assurance in advanced radiotherapy techniques.

PubMed

Togno, M; Wilkens, J J; Menichelli, D; Oechsner, M; Perez-Andujar, A; Morin, O

2016-05-01

To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm(3). The detector has been characterized with (60)Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both the source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, -0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09-2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm(2), the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm(2) field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm(2) field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Togno, M., E-mail: michele.togno@iba-group.com; Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Munich 81675; IBA Dosimetry GmbH, Schwarzenbruck 90592

Purpose: To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. Methods: The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm{sup 3}. The detector has been characterized with {sup 60}Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both themore » source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. Results: Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, −0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09–2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm{sup 2}, the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm{sup 2} field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm{sup 2} field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. Conclusions: The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.« less

Feasibility study of glass dosimeter postal dosimetry audit of high-energy radiotherapy photon beams.

PubMed

Mizuno, Hideyuki; Kanai, Tatsuaki; Kusano, Yohsuke; Ko, Susumu; Ono, Mari; Fukumura, Akifumi; Abe, Kyoko; Nishizawa, Kanae; Shimbo, Munefumi; Sakata, Suoh; Ishikura, Satoshi; Ikeda, Hiroshi

2008-02-01

The characteristics of a glass dosimeter were investigated for its potential use as a tool for postal dose audits. Reproducibility, energy dependence, field size and depth dependence were compared to those of a thermoluminescence dosimeter (TLD), which has been the major tool for postal dose audits worldwide. A glass dosimeter, GD-302M (Asahi Techno Glass Co.) and a TLD, TLD-100 chip (Harshaw Co.) were irradiated with gamma-rays from a (60)Co unit and X-rays from a medical linear accelerator (4, 6, 10 and 20 MV). The dosimetric characteristics of the glass dosimeter were almost equivalent to those of the TLD, in terms of utility for dosimetry under the reference condition, which is a 10 x 10 cm(2) field and 10 cm depth. Because of its reduced fading, compared to the TLD, and easy quality control with the ID number, the glass dosimeter proved to be a suitable tool for postal dose audits. Then, we conducted postal dose surveys of over 100 facilities and got good agreement, with a standard deviation of about 1.3%. Based on this study, postal dose audits throughout Japan will be carried out using a glass dosimeter.

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

NASA Technical Reports Server (NTRS)

Chappelli, Lori J.; Cucinotta, Francis A.

2010-01-01

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions

NASA Technical Reports Server (NTRS)

Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Takai, N.; Wu, H.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

2001-01-01

PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.

Cancer risk above 1 Gy and the impact for space radiation protection

NASA Astrophysics Data System (ADS)

Schneider, Uwe; Walsh, Linda

2009-07-01

Analyses of the epidemiological data on the Japanese A-bomb survivors, who were exposed to γ-rays and neutrons, provide most current information on the dose-response of radiation-induced cancer. Since the dose span of main interest is usually between 0 and 1 Gy, for radiation protection purposes, the analysis of the A-bomb survivors is often focused on this range. However, estimates of cancer risk for doses larger than 1 Gy are becoming more important for long-term manned space missions. Therefore in this work, emphasis is placed on doses larger than 1 Gy with respect to radiation-induced solid cancer and leukemia mortality. The present analysis of the A-bomb survivors data was extended by including two extra high-dose categories and applying organ-averaged dose instead of the colon-weighted dose. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear and a linear-exponential dose-response relationship using a dose and dose-rate effectiveness factor (DDREF) of both one and two. The work presented here implies that the use of organ-averaged dose, a dose-dependent neutron RBE and the bending-over of the dose-response relationship for radiation-induced cancer could result in a reduction of radiation risk by around 50% above 1 Gy. This could impact radiation risk estimates for space crews on long-term mission above 500 days who might be exposed to doses above 1 Gy. The consequence of using a DDREF of one instead of two increases cancer risk by about 40% and would therefore balance the risk decrease described above.

A novel synthetic single crystal diamond device for in vivo dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marinelli, Marco; Prestopino, G., E-mail: giuseppe.prestopino@uniroma2.it; Tonnetti, A.

Purpose: Aim of the present work is to evaluate the synthetic single crystal diamond Schottky photodiode developed at the laboratories of “Tor Vergata” University in Rome in a new dosimeter configuration specifically designed for offline wireless in vivo dosimetry (IVD) applications. Methods: The new diamond based dosimeter, single crystal diamond detector (SCDD-iv), consists of a small unwired detector and a small external reading unit that can be connected to commercial electrometers for getting the detector readout after irradiation. Two nominally identical SCDD-iv dosimeter prototypes were fabricated and tested. A basic dosimetric characterization of detector performances relevant for IVD application wasmore » performed under irradiation with {sup 60}Co and 6 MV photon beams. Preirradiation procedure, response stability, short and long term reproducibility, leakage charge, fading effect, linearity with dose, dose rate dependence, temperature dependence, and angular response were investigated. Results: The SCDD-iv is simple, with no cables linked to the patient and the readout is immediate. The range of response with dose has been tested from 1 up to 12 Gy; the reading is independent of the accumulated dose and dose rate independent in the range between about 0.5 and 5 Gy/min; its temperature dependence is within 0.5% between 25 and 38 °C, and its directional dependence is within 2% from 0° to 90°. The combined relative standard uncertainty of absorbed dose to water measurements is estimated lower than the tolerance and action level of 5%. Conclusions: The reported results indicate the proposed novel offline dosimeter based on a synthetic single crystal diamond Schottky photodiode as a promising candidate for in vivo dosimetry applications with photon beams.« less

A novel synthetic single crystal diamond device for in vivo dosimetry.

PubMed

Marinelli, Marco; Prestopino, G; Tonnetti, A; Verona, C; Verona-Rinati, G; Falco, M D; Bagalà, P; Pimpinella, M; Guerra, A S; De Coste, V

2015-08-01

Aim of the present work is to evaluate the synthetic single crystal diamond Schottky photodiode developed at the laboratories of "Tor Vergata" University in Rome in a new dosimeter configuration specifically designed for offline wireless in vivo dosimetry (IVD) applications. The new diamond based dosimeter, single crystal diamond detector (SCDD-iv), consists of a small unwired detector and a small external reading unit that can be connected to commercial electrometers for getting the detector readout after irradiation. Two nominally identical SCDD-iv dosimeter prototypes were fabricated and tested. A basic dosimetric characterization of detector performances relevant for IVD application was performed under irradiation with (60)Co and 6 MV photon beams. Preirradiation procedure, response stability, short and long term reproducibility, leakage charge, fading effect, linearity with dose, dose rate dependence, temperature dependence, and angular response were investigated. The SCDD-iv is simple, with no cables linked to the patient and the readout is immediate. The range of response with dose has been tested from 1 up to 12 Gy; the reading is independent of the accumulated dose and dose rate independent in the range between about 0.5 and 5 Gy/min; its temperature dependence is within 0.5% between 25 and 38 °C, and its directional dependence is within 2% from 0° to 90°. The combined relative standard uncertainty of absorbed dose to water measurements is estimated lower than the tolerance and action level of 5%. The reported results indicate the proposed novel offline dosimeter based on a synthetic single crystal diamond Schottky photodiode as a promising candidate for in vivo dosimetry applications with photon beams.

Impact of the Nationwide Intravenous Selenium Product Shortage on the Development of Selenium Deficiency in Infants Dependent on Long-Term Parenteral Nutrition.

PubMed

Chen, Connie H; Harris, Mary Beth; Partipilo, M Luisa; Welch, Kathleen B; Teitelbaum, Daniel H; Blackmer, Allison B

2016-08-01

For patients dependent on parenteral nutrition (PN), selenium must be supplemented intravenously. A nationwide intravenous selenium shortage began in April 2011. The impact of this shortage on PN-dependent infants was evaluated by examining the provision of selenium, development of biochemical deficiency, and costs associated with the shortage. This single-center, retrospective study included PN-dependent infants aged ≤1 year who weighed ≤30 kg, received PN for ≥1 month, and had ≥1 serum selenium measurement. The primary outcome was the incidence of biochemical selenium deficiency. Secondary outcomes included severity of biochemical deficiency, clinical manifestations, costs, and relationship between serum selenium levels and selenium dose. The average selenium dose decreased 2-fold during the shortage (2.1 ± 1.2 µg/kg/d; range, 0.2-4.6 µg/kg/d) versus the nonshortage period (3.8 ± 1 µg/kg/d; range, 2.4-6 µg/kg/d; P < .001). A linear relationship between serum selenium concentration and selenium dose was observed (r(2) = 0.42), with a dose of 6 µg/kg/d expected to result in normal serum levels in most cases. Similar proportions of patients developed biochemical deficiency in both groups: shortage period, 59.1%; nonshortage, 66.7%; P = .13. The severity of biochemical deficiency was similar between groups. A significant increase in incremental cost during the shortage was observed. This is the first study examining the impact of the intravenous selenium shortage on PN-dependent infants. Both groups exhibited similarly high incidences of biochemical selenium deficiency, suggesting higher empiric doses may benefit this population. However, ongoing shortages limit the ability to provide supplementation. © 2015 American Society for Parenteral and Enteral Nutrition.

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.

PubMed

Wyrobek, Andrew J; Britten, Richard A

2016-06-01

Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Linear response of mutans streptococci to increasing frequency of xylitol chewing gum use: a randomized controlled trial [ISRCTN43479664].

PubMed

Ly, Kiet A; Milgrom, Peter; Roberts, Marilyn C; Yamaguchi, David K; Rothen, Marilynn; Mueller, Greg

2006-03-24

Xylitol is a naturally occurring sugar substitute that has been shown to reduce the level of mutans streptococci in plaque and saliva and to reduce tooth decay. It has been suggested that the degree of reduction is dependent on both the amount and the frequency of xylitol consumption. For xylitol to be successfully and cost-effectively used in public health prevention strategies dosing and frequency guidelines should be established. This study determined the reduction in mutans streptococci levels in plaque and unstimulated saliva to increasing frequency of xylitol gum use at a fixed total daily dose of 10.32 g over five weeks. Participants (n = 132) were randomized to either active groups (10.32 g xylitol/day) or a placebo control (9.828 g sorbitol and 0.7 g maltitol/day). All groups chewed 12 pieces of gum per day. The control group chewed 4 times/day and active groups chewed xylitol gum at a frequency of 2 times/day, 3 times/day, or 4 times/day. The 12 gum pieces were evenly divided into the frequency assigned to each group. Plaque and unstimulated saliva samples were taken at baseline and five-weeks and were cultured on modified Mitis Salivarius agar for mutans streptococci enumeration. There were no significant differences in mutans streptococci level among the groups at baseline. At five-weeks, mutans streptococci levels in plaque and unstimulated saliva showed a linear reduction with increasing frequency of xylitol chewing gum use at the constant daily dose. Although the difference observed for the group that chewed xylitol 2 times/day was consistent with the linear model, the difference was not significant. There was a linear reduction in mutans streptococci levels in plaque and saliva with increasing frequency of xylitol gum use at a constant daily dose. Reduction at a consumption frequency of 2 times per day was small and consistent with the linear-response line but was not statistically significant.

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Dosimetric characterization of optically stimulated luminescence dosimeter with therapeutic photon beams for use in clinical radiotherapy measurements.

PubMed

Ponmalar, Retna; Manickam, Ravikumar; Ganesh, K M; Saminathan, Sathiyan; Raman, Arun; Godson, Henry Finlay

2017-01-01

The modern radiotherapy techniques impose new challenges for dosimetry systems with high precision and accuracy in in vivo and in phantom dosimetric measurements. The knowledge of the basic characterization of a dosimetric system before patient dose verification is crucial. This incites the investigation of the potential use of nanoDot optically stimulated luminescence dosimeter (OSLD) for application in radiotherapy with therapeutic photon beams. Measurements were carried out with nanoDot OSLDs to evaluate the dosimetric characteristics such as dose linearity, dependency on field size, dose rate, energy and source-to-surface distance (SSD), reproducibility, fading effect, reader stability, and signal depletion per read out with cobalt-60 (60 Co) beam, 6 and 18 MV therapeutic photon beams. The data acquired with OSLDs were validated with ionization chamber data where applicable. Good dose linearity was observed for doses up to 300 cGy and above which supralinear behavior. The standard uncertainty with field size observed was 1.10% ± 0.4%, 1.09% ± 0.34%, and 1.2% ± 0.26% for 6 MV, 18 MV, and 60 Co beam, respectively. The maximum difference with dose rate was 1.3% ± 0.4% for 6 MV and 1.4% ± 0.4% for 18 MV photon beams. The largest variation in SSD was 1.5% ± 1.2% for 60 Co, 1.5% ± 0.9% for 6 MV, and 1.5% ± 1.3% for 18 MV photon beams. The energy dependence of OSL response at 18 MV and 60 Co with 6 MV beam was 1.5% ± 0.7% and 1.7% ± 0.6%, respectively. In addition, good reproducibility, stability after the decay of transient signal, and predictable fading were observed. The results obtained in this study indicate the efficacy and suitability of nanoDot OSLD for dosimetric measurements in clinical radiotherapy.

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.

PubMed

Ramos, Alga S; Seip, Richard L; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F; Cadilla, Carmen L; Renta, Jessica Y; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

2012-12-01

This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R(2) = 51%). Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients.

Patient dose, gray level and exposure index with a computed radiography system

NASA Astrophysics Data System (ADS)

Silva, T. R.; Yoshimura, E. M.

2014-02-01

Computed radiography (CR) is gradually replacing conventional screen-film system in Brazil. To assess image quality, manufactures provide the calculation of an exposure index through the acquisition software of the CR system. The objective of this study is to verify if the CR image can be used as an evaluator of patient absorbed dose too, through a relationship between the entrance skin dose and the exposure index or the gray level values obtained in the image. The CR system used for this study (Agfa model 30-X with NX acquisition software) calculates an exposure index called Log of the Median (lgM), related to the absorbed dose to the IP. The lgM value depends on the average gray level (called Scan Average Level (SAL)) of the segmented pixel value histogram of the whole image. A Rando male phantom was used to simulate a human body (chest and head), and was irradiated with an X-ray equipment, using usual radiologic techniques for chest exams. Thermoluminescent dosimeters (LiF, TLD100) were used to evaluate entrance skin dose and exit dose. The results showed a logarithm relation between entrance dose and SAL in the image center, regardless of the beam filtration. The exposure index varies linearly with the entrance dose, but the angular coefficient is beam quality dependent. We conclude that, with an adequate calibration, the CR system can be used to evaluate the patient absorbed dose.

Testing and linearity calibration of films of phenol compounds exposed to thermal neutron field for EPR dosimetry.

PubMed

Gallo, S; Panzeca, S; Longo, A; Altieri, S; Bentivoglio, A; Dondi, D; Marconi, R P; Protti, N; Zeffiro, A; Marrale, M

2015-12-01

This paper reports the preliminary results obtained by Electron Paramagnetic Resonance (EPR) measurements on films of IRGANOX® 1076 phenols with and without low content (5% by weight) of gadolinium oxide (Gd2O3) exposed in the thermal column of the Triga Mark II reactor of LENA (Laboratorio Energia Nucleare Applicata) of Pavia (Italy). Thanks to their size, the phenolic films here presented are good devices for the dosimetry of beams with high dose gradient and which require accurate knowledge of the precise dose delivered. The dependence of EPR signal as function of neutron dose was investigated in the fluence range between 10(11) cm(-2) and 10(14) cm(-2). Linearity of EPR response was found and the signal was compared with that of commercial alanine films. Our analysis showed that gadolinium oxide (5% by weight) can enhance the thermal neutron sensitivity more than 18 times. Irradiated dosimetric films of phenolic compound exhibited EPR signal fading of about 4% after 10 days from irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.

PubMed

Milman, Garry; Bergamaschi, Mateus M; Lee, Dayong; Mendu, Damodara R; Barnes, Allan J; Vandrey, Ryan; Huestis, Marilyn A

2014-04-01

Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH. During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking. The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.

Plasma Cannabinoid Concentrations during Dronabinol Pharmacotherapy for Cannabis Dependence

PubMed Central

Milman, Garry; Bergamaschi, Mateus M.; Lee, Dayong; Mendu, Damodara R.; Barnes, Allan J.; Vandrey, Ryan; Huestis, Marilyn A.

2013-01-01

Background Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic daily cannabis smokers who received high-dose oral THC pharmacotherapy and later, a smoked cannabis challenge. Methods 11 daily cannabis smokers received 0, 30, 60, or 120 mg/day THC for four 5-day medication sessions, each separated by 9-days of ad-libitum cannabis smoking. On the 5th day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the 1st and 5th days was quantified by GC-GC-MS for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5–100 for THC, 1–50 11-OH-THC, and 0.5–200 THCCOOH. Results During placebo dosing, THC, 11-OH-THC and THCCOOH concentrations consistently decreased, while all cannabinoids increased dose-dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during 60 and 120 mg/day doses, and THCCOOH increased significantly only during the 120 mg/day dose. THC and 11-OH-THC, and THCCOOH concentrations peaked within 0.25 h after cannabis smoking, except after 120 mg/day THC when THCCOOH peaked 0.5 h before smoking. Conclusions The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 h, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 h after overnight oral dronabinol abstinence, but cannot distinguish oral THC dosing from smoked cannabis intake. PMID:24067260

[Cytogenetic effects of low dose radiation with different LET in human peripheral blood lymphocytes and possible mechanisms of their realization].

PubMed

Nasonova, E A; Shmakova, N L; Komova, O V; Mel'nikova, L A; Fadeeva, T A; Krasavin, E A

2006-01-01

The induction of chromosome damage by the exposure to low doses of gamma-(60)Co and accelerated carbon ions 12C in peripheral blood lymphocytes of different donors was investigated. The complex nonlinear dose-effect dependence at the range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type aberration, which is typical to those spontaneously generated in the cell and believed not to be induced by the irradiation of unstimulated lymphocytes according to the classical theory of aberration formation. With the increasing dose the frequency of the aberrations decreases significantly, in some cases up to the control level. At the doses over 50-70 cGy the dose-effect curve becomes linear. The possible role of the oxidative stress, caused by radiation-induced increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon of hypersensitivity (HS) at low doses is discussed as well as cytoprotective mechanisms causing the increased radioresistance at higher doses.

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Śliwka, Przemysław W; Puła, Bartosz; Karwowski, Bolesław; Merecz-Sadowska, Anna; Dedecjus, Marek; Lewiński, Andrzej

2017-06-15

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131 I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131 I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations ( p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131 I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of Intensity-Modulated Pelvic Radiotherapy on Second Cancer Risk in the Postoperative Treatment of Endometrial and Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zwahlen, Daniel R.; Department of Radiation Oncology, University Hospital Zurich, Zurich; Ruben, Jeremy D.

2009-06-01

Purpose: To estimate and compare intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3DCRT) in terms of second cancer risk (SCR) for postoperative treatment of endometrial and cervical cancer. Methods and Materials: To estimate SCR, the organ equivalent dose concept with a linear-exponential, a plateau, and a linear dose-response model was applied to dose distributions, calculated in a planning computed tomography scan of a 68-year-old woman. Three plans were computed: four-field 18-MV 3DCRT and nine-field IMRT with 6- and 18-MV photons. SCR was estimated as a function of target dose (50.4 Gy/28 fractions) in organs of interest according to the Internationalmore » Commission on Radiological Protection Results: Cumulative SCR relative to 3DCRT was +6% (3% for a plateau model, -4% for a linear model) for 6-MV IMRT and +26% (25%, 4%) for the 18-MV IMRT plan. For an organ within the primary beam, SCR was +12% (0%, -12%) for 6-MV and +5% (-2%, -7%) for 18-MV IMRT. 18-MV IMRT increased SCR 6-7 times for organs away from the primary beam relative to 3DCRT and 6-MV IMRT. Skin SCR increased by 22-37% for 6-MV and 50-69% for 18-MV IMRT inasmuch as a larger volume of skin was exposed. Conclusion: Cancer risk after IMRT for cervical and endometrial cancer is dependent on treatment energy. 6-MV pelvic IMRT represents a safe alternative with respect to SCR relative to 3DCRT, independently of the dose-response model. 18-MV IMRT produces second neutrons that modestly increase the SCR.« less

Analysis of pharmacokinetics of Gd-DTPA for dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Taheri, Saeid; Shah, N Jon; Rosenberg, Gary A

2016-09-01

The pharmacokinetics (PK) of the contrast agent Gd-DTPA administered intravenously (i.v.) for contrast-enhanced MR imaging (DCE-MRI) is an important factor for quantitative data acquisition. We studied the effect of various initial bolus doses on the PK of Gd-DTPA and analyzed population PK of a lower dose for intra-subject variations in DCE-MRI. First, fifteen subjects (23-85years, M/F) were randomly divided into four groups for DCE-MRI with different Gd-DTPA dose: group-I, 0.1mmol/kg, n=4; group-II, 0.05mmol/kg, n=4; group-III, 0.025mmol/kg, n=4; and group-IV, 0.0125mmol/kg, n=3. Sequential fast T1 mapping sequence, after a bolus i.v. Gd-DTPA administered, and a linear T1-[Gd-DTPA] relationship were used to estimate the PK of Gd-DTPA. Secondly, MR-acquired PKs of Gd-DTPA from 58 subjects (28-80years, M/F) were collected retrospectively, from an ongoing study of the brain using DCE-MRI with Gd-DTPA at 0.025mmol/kg, to statistically analyze population PK of Gd-DTPA. We found that the PK of Gd-DTPA (i.v. 0.025mmol/kg) had a half-life of 37.3±6.6min, and was a better fit into a linear T1-[Gd-DTPA] relationship than higher doses (up to 0.1mmol/kg). The area under the curve (AUC) for 0.025mmol/kg was 3.37±0.46, which was a quarter of AUC of 0.1mmol/kg. In population analysis, a dose of 0.025mmol/kg of Gd-DTPA provided less than 5% subject-dependent variation in the PK of Gd-DTPA. Administration of 0.025mmol/kg Gd-DTPA enabled us to estimate [Gd-DTPA] from T1 by using a linear relationship that has a lower estimation error compared to a non-linear relationship. DCE-MRI with a quarter dose of Gd-DTPA is more sensitive to detect changes in [Gd-DTPA]. Copyright © 2016 Elsevier Inc. All rights reserved.

TH-AB-BRA-06: MOSFET-Based Dosimetry in An MR Image-Guided Radiation Therapy System: Comparison with and Without a Static 0.3T Magnetic Field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cammin, J; Curcuru, A; Li, H

Purpose: To compare depth-dose and surface-dose measurements without and with the magnetic field in a 0.3T MR image-guided Co-60 treatment unit using MOSFET dosimeters. Methods: MOSFET dosimeters (Best Medical Canada, model TN-502RDH-10) were placed in a solid water phantom at 5cm depth with 8cm backscatter (with the MOSFET wires in different orientations to the couch long axis) and also on the surface of an 8cm solid water phantom. The phantoms were placed in an MR image-guided Co-60 treatment machine at an SAD of 105cm to the MOSFETs. Dose measurements were performed between 50 and 200cGy at 5cm depth in amore » 10.5cm × 10.5cm radiation field without the magnetic field (during a machine maintenance period) and with the nominal magnetic field of 0.3T. The dose linearity was measured at 5cm depth with an orthogonal field and the angular dose dependence was measured on the surface with an orthogonal field and oblique fields at +60 degrees and −60 degrees. Results: The measured MOSFET readings at 5cm depth were linear with dose with slopes of (2.97 +/− 0.01) mV/cGy and (3.01 +/− 0.02) mV/cGy without and with the magnetic field, respectively. No statistically significant difference was found. The surface dose measurements, however, were lower by 6.4% for the AP field (2.3 σ) with magnetic field, 4.9% for the −60 degree field (1.4 σ), and 0.4% different for the +60 degree field (0.2 σ). Conclusion: There is no statistically significant difference in the dose at depth without and with the magnetic field and different orientations of the MOSFET wires. There is a statistically significant difference for the surface dose due to the influence of the magnetic field on secondary electrons from head-scatter and the build-up region in certain field orientations. Clinical surface-dose dosimetry in a magnetic field should apply asymmetric angle-dependent corrections.« less

Accounting for neutron exposure in the Japanese atomic bomb survivors.

PubMed

Cullings, Harry M; Pierce, Donald A; Kellerer, Albrecht M

2014-12-01

The Japanese atomic bomb survivors that were directly exposed to both γ rays and neutrons have been followed by the Radiation Effects Research Foundation (RERF). The estimation of the γ-ray risks requires some adjustment for the greater biological effect of the neutrons per unit dose. Because the small neutron doses and the predominant γ-ray doses are highly correlated, the neutron relative biological effectiveness (RBE) cannot be reliably estimated from the survivors' data and information from radiobiology must be invoked. As data became available on neutron doses, RERF has used a constant neutron RBE value of 10, even though radiobiological studies indicate that the RBE values appear to have considerably larger values at low doses. The approximation RBE = 10 assumes that if the RBE is variable it takes roughly this value in the range of total dose most relevant for linear risk estimation, namely about 1 Gy. We consider some possible RBE functions to explain the correct use and the impact of a dose-dependent RBE. However, we do not advocate any particular choice or even that a variable RBE be employed. Rather we show that the assumed neutron RBE, within a wide range of choices, is far less important to the outcome of risk assessment of the RERF data than generally believed. Some of these misperceptions have been related to the consideration of variable RBE functions, and without due attention to the fact that in the case of the A-bomb survivors' data, the mixed field of neutrons and γ rays must be considered. Therefore, the RBE value of neutrons is much lower than the RBE in pure neutron fields that are used in radiobiological experiments. Thus, applying the pure neutron field RBE to the mixed-field A-bomb radiation can lead to an overestimation of the actual neutron RBE for moderate total dose levels of 1 Gy by a factor of more than four. While in a pure neutron exposure the RBE depends on the neutron dose, in the mixed field it depends on both components of exposure, and in particular, we show that in the RERF setting the RBE depends mainly on the accompanying γ-ray dose.

Thermoluminescence properties of gamma-irradiated nano-structure hydroxyapatite.

PubMed

Shafaei, M; Ziaie, F; Sardari, D; Larijani, M M

2016-02-01

The suitability of nano-structured hydroxyapatite (HAP) for use as a thermoluminescence dosimeter was investigated. HAP samples were synthesized using a hydrolysis method. The formation of nanoparticles was confirmed by X-ray diffraction and average particle size was estimated to be ~30 nm. The glow curve exhibited a peak centered at around 200 °C. The additive dose method was applied and this showed that the thermoluminescence (TL) glow curves follow first-order kinetics due to the non-shifting nature of Tm after different doses. The numbers of overlapping peaks and related kinetic parameters were identified from Tm -Tstop through computerized glow curve deconvolution methods. The dependence of the TL responses on radiation dose was studied and a linear dose response up to 1000 Gy was observed for the samples. Copyright © 2015 John Wiley & Sons, Ltd.

Depth dependence of absorbed dose, dose equivalent and linear energy transfer spectra of galactic and trapped particles in polyethylene and comparison with calculations of models

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cucinotta, F. A.; Wilson, J. W. (Principal Investigator)

1998-01-01

A matched set of five tissue-equivalent proportional counters (TEPCs), embedded at the centers of 0 (bare), 3, 5, 8 and 12-inch-diameter polyethylene spheres, were flown on the Shuttle flight STS-81 (inclination 51.65 degrees, altitude approximately 400 km). The data obtained were separated into contributions from trapped protons and galactic cosmic radiation (GCR). From the measured linear energy transfer (LET) spectra, the absorbed dose and dose-equivalent rates were calculated. The results were compared to calculations made with the radiation transport model HZETRN/NUCFRG2, using the GCR free-space spectra, orbit-averaged geomagnetic transmission function and Shuttle shielding distributions. The comparison shows that the model fits the dose rates to a root mean square (rms) error of 5%, and dose-equivalent rates to an rms error of 10%. Fairly good agreement between the LET spectra was found; however, differences are seen at both low and high LET. These differences can be understood as due to the combined effects of chord-length variation and detector response function. These results rule out a number of radiation transport/nuclear fragmentation models. Similar comparisons of trapped-proton dose rates were made between calculations made with the proton transport model BRYNTRN using the AP-8 MIN trapped-proton model and Shuttle shielding distributions. The predictions of absorbed dose and dose-equivalent rates are fairly good. However, the prediction of the LET spectra below approximately 30 keV/microm shows the need to improve the AP-8 model. These results have strong implications for shielding requirements for an interplanetary manned mission.

Nicotine abstinence syndrome precipitated by central but not peripheral hexamethonium.

PubMed

Malin, D H; Lake, J R; Schopen, C K; Kirk, J W; Sailer, E E; Lawless, B A; Upchurch, T P; Shenoi, M; Rajan, N

1997-11-01

A rodent model of nicotine dependence has been developed based on continuous subcutaneous (s.c.) infusion of nicotine tartrate. Nicotine abstinence syndrome was precipitated by s.c. injection of the nicotinic antagonist mecamylamine, which freely crosses the blood-brain barrier. In contrast, the nicotinic antagonist hexamethonium crosses the blood-brain barrier very poorly. This study determined whether central or peripheral administration of hexamethonium could precipitate nicotine abstinence. In the first experiment, 26 nicotine-dependent rats were injected s.c. with 0.5, 5 or 10 mg/kg hexamethonium dichloride or saline alone and observed for 20 min. Few abstinence signs were observed in any group; there was no significant drug effect. In the second experiment, 18 rats were cannulated in the third ventricle and rendered nicotine dependent. One week later, rats were injected through the cannula with 12 or 18 ng hexamethonium or saline alone and observed for 20 min. Both dose groups differed significantly from the saline-injected group, and there was a significant positive linear trend of signs as a function of dose. The high dose had no significant effect in 14 nondependent rats. We conclude that hexamethonium is much more potent by the central route, and there is a major central nervous system component in nicotine dependence.

Calibration of GafChromic EBT3 for absorbed dose measurements in 5 MeV proton beam and (60)Co γ-rays.

PubMed

Vadrucci, M; Esposito, G; Ronsivalle, C; Cherubini, R; Marracino, F; Montereali, R M; Picardi, L; Piccinini, M; Pimpinella, M; Vincenti, M A; De Angelis, C

2015-08-01

To study EBT3 GafChromic film in low-energy protons, and for comparison purposes, in a reference (60)Co beam in order to use it as a calibrated dosimetry system in the proton irradiation facility under construction within the framework of the Oncological Therapy with Protons (TOP)-Intensity Modulated Proton Linear Accelerator for RadioTherapy (IMPLART) Project at ENEA-Frascati, Italy. EBT3 film samples were irradiated at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Legnaro, Italy, with a 5 MeV proton beam generated by a 7 MV Van de Graaff CN accelerator. The nominal dose rates used were 2.1 Gy/min and 40 Gy/min. The delivered dose was determined by measuring the particle fluence and the energy spectrum in air with silicon surface barrier detector monitors. A preliminary study of the EBT3 film beam quality dependence in low-energy protons was conducted by passively degrading the beam energy. EBT3 films were also irradiated at ENEA-National Institute of Ionizing Radiation Metrology with gamma radiation produced by a (60)Co source characterized by an absorbed dose to water rate of 0.26 Gy/min as measured by a calibrated Farmer type ionization chamber. EBT3 film calibration curves were determined by means of a set of 40 film pieces irradiated to various doses ranging from 0.5 Gy to 30 Gy absorbed dose to water. An EPSON Expression 11000XL color scanner in transmission mode was used for film analysis. Scanner response stability, intrafilm uniformity, and interfilm reproducibility were verified. Optical absorption spectra measurements were performed on unirradiated and irradiated EBT3 films to choose the most sensitive color channel to the dose range used. EBT3 GafChromic films show an under response up to about 33% for low-energy protons with respect to (60)Co gamma radiation, which is consistent with the linear energy transfer dependence already observed with higher energy protons, and a negligible dose-rate dependence in the 2-40 Gy/min range. Short- and long-term scanner stabilities were 0.5% and 1.5%, respectively; film uniformity and reproducibility were better than 0.5%. The main purpose of this study was to implement EBT3 dosimetry in the proton low-energy radiobiology line of the TOP-IMPLART accelerator, having a maximum energy of 7 MeV. Low-energy proton and (60)Co calibrated sources were used to investigate the behavior of film response vs to be written in italicum dose. The calibration in 5 MeV protons is currently used for dose assessment in the radiobiological experiments at the TOP-IMPLART accelerator carried out at that energy value.

High dose-per-pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use.

PubMed

Jaccard, Maud; Durán, Maria Teresa; Petersson, Kristoffer; Germond, Jean-François; Liger, Philippe; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François; Bailat, Claude

2018-02-01

The Oriatron eRT6 is an experimental high dose-per-pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose-rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose-per-pulse/dose-rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac. The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose-rate and one with a much higher dose-rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator. The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non-negligible day-to-day variations of the beam output were observed. Those output variations showed different trends depending on the dose-rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose-rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose-rate-dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom. The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose-per-pulse irradiation. © 2017 American Association of Physicists in Medicine.

Characteristics of fiber-optic radiation sensor for passive scattering proton beams

NASA Astrophysics Data System (ADS)

Son, J.; Kim, M.; Jeong, J.; Lim, Y.; Lee, S. B.; Shin, D.; Yoon, M.

2017-11-01

The aims of this study were to investigate the characteristics of a fiber-optic radiation sensor (FORS) that detects the fluorescence light produced by proton beam and to verify its effectiveness in proton therapy quality assurance (QA). Various characteristics of the FORS were investigated, such as the linearity of its relationships to the sensitive length of fiber for the proton beams of intermediate ranges (165.46 and 178.37 MeV) and to the measured dose, as well as its dose rate dependence. In addition, patient specific precription dose QA was conducted for five patients actually undergoing proton therapy and the results were compared with the doses measured using an ion chamber. The results show that the signal of the FORS is linearly related to the sensitive length of fiber and to the irradiated dose in the range from 1 to 500 cGy. The QA results obtained using the FORS system showed good agreement with the corresponding ion chamber results, with an average difference of 0.40% and a standard deviation of 0.35%. The FORS was dose-rate independent for proton currents up to 5 Gy/min. The profiles of various proton beams obtained using an array of FORS, which were measured as an application of the developed dosimetric system, closely agreed with the profiles acquired using EBT3 film. In summary, the experimental results of FORS demonstrated its effectiveness for use in various proton therapy QA tests.

Dosimetric characterization and behaviour in small X-ray fields of a microchamber and a plastic scintillator detector.

PubMed

Pasquino, Massimo; Cutaia, Claudia; Radici, Lorenzo; Valzano, Serena; Gino, Eva; Cavedon, Carlo; Stasi, Michele

2017-01-01

The aim of this work was to investigate the main dosimetric characteristics and the performance of an A26 Exradin ionization microchamber (A26 IC) and a W1 Exradin plastic scintillation detector (W1 PSD) in small photon beam dosimetry for treatment planning system commissioning and quality assurance programme. Detector characterization measurements (short-term stability, dose linearity, angular dependence and energy dependence) were performed in water for field sizes up to 10 × 10 cm 2 . Polarity effect (P pol ) was examined for the A26 IC. The behaviour of the detectors in small field relative dosimetry [percentage depth dose, dose profiles often called the off-axis ratio and output factors (OFs)] was investigated for field sizes ranging from 1 × 1 to 3 × 3 cm 2 . Results were compared with those obtained with other detectors we already use for small photon beam dosimetry. A26 IC and W1 PSD showed a linear dose response. While the A26 IC showed no energy dependence, the W1 PSD showed energy dependence within 2%; no angular dependence was registered. P pol values for A26 IC were below 0.9% (0.5% for field size >2 × 2 cm 2 ). A26 IC and W1 PSD depth-dose curves and lateral profiles agreed with those obtained with an EDGE diode. No differences were observed among the detectors in OF measurement for field sizes larger than 1 × 1 cm 2 , with average differences <1%. For field sizes <1 × 1 cm 2 , the effective volume of ionization chamber and non-water equivalence of EDGE diode become significant. A26 IC OF values were significantly lower than EDGE diode and W1 PSD values, with percentage differences of about -23 and -13% for the smallest field, respectively. W1 PSD OF values lay between ion chambers and diode values, with a maximum percentage difference of about -10% with respect to the EDGE diode, for a 6 × 6-mm 2 field size. The results of our investigation confirm that A26 IC and W1 PSD could play an important role in small field relative dosimetry. Advances in knowledge: Dosimetric characteristics of Exradin A26 ionization microchamber and W1 plastic scintillation detector for small field dosimetry.

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

PubMed

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

2D dosimetry in a proton beam with a scintillating GEM detector

NASA Astrophysics Data System (ADS)

Seravalli, E.; de Boer, M. R.; Geurink, F.; Huizenga, J.; Kreuger, R.; Schippers, J. M.; van Eijk, C. W. E.

2009-06-01

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for pre-treatment verification of dose distributions in particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF4 scintillating gas mixture, inside which two gas electron multiplier (GEM) structures are mounted (Seravalli et al 2008b Med. Phys. Biol. 53 4651-65). Photons emitted by the excited Ar/CF4 gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD camera system. The intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the characterization of the scintillating GEM detector in terms of those properties that are of particular importance in relative dose measurements, e.g. response reproducibility, dose dependence, dose rate dependence, spatial and time response, field size dependence, response uniformity. The experiments were performed in a 150 MeV proton beam. We found that the detector response is very stable for measurements performed in succession (σ = 0.6%) and its response reproducibility over 2 days is about 5%. The detector response was found to be linear with the dose in the range 0.05-19 Gy. No dose rate effects were observed between 1 and 16 Gy min-1 at the shallow depth of a water phantom and 2 and 38 Gy min-1 at the Bragg peak depth. No field size effects were observed in the range 120-3850 mm2. A signal rise and fall time of 2 µs was recorded and a spatial response of <=1 mm was measured.

Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams

NASA Astrophysics Data System (ADS)

Moignier, Cyril; Tromson, Dominique; de Marzi, Ludovic; Marsolat, Fanny; García Hernández, Juan Carlos; Agelou, Mathieu; Pomorski, Michal; Woo, Romuald; Bourbotte, Jean-Michel; Moignau, Fabien; Lazaro, Delphine; Mazal, Alejandro

2017-07-01

The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (e AV) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small e AV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0-5.5 Gy min-1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90-160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate dependence.

Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams.

PubMed

Moignier, Cyril; Tromson, Dominique; de Marzi, Ludovic; Marsolat, Fanny; García Hernández, Juan Carlos; Agelou, Mathieu; Pomorski, Michal; Woo, Romuald; Bourbotte, Jean-Michel; Moignau, Fabien; Lazaro, Delphine; Mazal, Alejandro

2017-07-07

The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (e AV ) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small e AV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0-5.5 Gy min -1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90-160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate dependence.

Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments.

PubMed

Ho, Lavine; White, Peter; Chan, Edward; Chan, Kim; Ng, Janet; Tam, Timothy

2012-01-01

Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. Two types of technique (anterior-posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. The highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.

Harderian Gland Tumorigenesis: Low-Dose and LET Response.

PubMed

Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

2016-05-01

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.

Harderian Gland Tumorigenesis: Low-Dose and LET Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Polly Y.; Cucinotta, Francis A.; Bjornstad, Kathleen A.

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSvmore » are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.« less

Characterization of the nanoDot OSLD dosimeter in CT.

PubMed

Scarboro, Sarah B; Cody, Dianna; Alvarez, Paola; Followill, David; Court, Laurence; Stingo, Francesco C; Zhang, Di; McNitt-Gray, Michael; Kry, Stephen F

2015-04-01

The extensive use of computed tomography (CT) in diagnostic procedures is accompanied by a growing need for more accurate and patient-specific dosimetry techniques. Optically stimulated luminescent dosimeters (OSLDs) offer a potential solution for patient-specific CT point-based surface dosimetry by measuring air kerma. The purpose of this work was to characterize the OSLD nanoDot for CT dosimetry, quantifying necessary correction factors, and evaluating the uncertainty of these factors. A characterization of the Landauer OSL nanoDot (Landauer, Inc., Greenwood, IL) was conducted using both measurements and theoretical approaches in a CT environment. The effects of signal depletion, signal fading, dose linearity, and angular dependence were characterized through direct measurement for CT energies (80-140 kV) and delivered doses ranging from ∼5 to >1000 mGy. Energy dependence as a function of scan parameters was evaluated using two independent approaches: direct measurement and a theoretical approach based on Burlin cavity theory and Monte Carlo simulated spectra. This beam-quality dependence was evaluated for a range of CT scanning parameters. Correction factors for the dosimeter response in terms of signal fading, dose linearity, and angular dependence were found to be small for most measurement conditions (<3%). The relative uncertainty was determined for each factor and reported at the two-sigma level. Differences in irradiation geometry (rotational versus static) resulted in a difference in dosimeter signal of 3% on average. Beam quality varied with scan parameters and necessitated the largest correction factor, ranging from 0.80 to 1.15 relative to a calibration performed in air using a 120 kV beam. Good agreement was found between the theoretical and measurement approaches. Correction factors for the measurement of air kerma were generally small for CT dosimetry, although angular effects, and particularly effects due to changes in beam quality, could be more substantial. In particular, it would likely be necessary to account for variations in CT scan parameters and measurement location when performing CT dosimetry using OSLD.

Characterization of a commercially-available, optically-stimulated luminescent dosimetry system for use in computed tomography.

PubMed

Lavoie, Lindsey; Ghita, Monica; Brateman, Libby; Arreola, Manuel

2011-09-01

Optically-stimulated luminescent (OSL) nanoDot dosimeters, commercially available from Landauer, Inc. (Glenwood, IL), were assessed for use in computed tomography (CT) for erasure and reusability, linearity and reproducibility of response, and angular and energy response in different scattering conditions. Following overnight exposure to fluorescent room light, the residual signal on the dosimeters was 2%. The response of the dosimeters to identical exposures was consistent, and reported doses were within 4% of each other. The dosimeters responded linearly with dose up to 1 Gy. The dosimeter response to the CT beams decreased with increased tube voltage, showing up to a -16% difference when compared to a 0.6-cm(3) NIST-traceable calibrated ionization chamber for a 135 kVp CT beam. The largest range in percent difference in dosimeter response to scatter at central and peripheral positions inside CTDI phantoms was 14% at 80 kVp CT tube voltage, when compared to the ionization chamber. The dosimeters responded uniformly to x-ray tube angle over the ranges of increments of 0° to 75° and 105° to 180° when exposed in air, and from 0° to 360° when exposed inside a CTDI phantom. While energy and scatter correction factors should be applied to dosimeter readings for the purpose of determining absolute doses, these corrections are straightforward but depend on the accuracy of the ionization chamber used for cross-calibration. The linearity and angular responses, combined with the ability to reuse the dosimeters, make this OSL system an excellent choice for clinical CT dose measurements.

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.

PubMed

Berns, G S; Song, A W; Mao, H

1999-07-15

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent.

Single ascending oral dose pharmacokinetics and pharmacodynamics study of EV-077: the specific inhibitor of prostanoid- and isoprostane-induced cellular activation.

PubMed

Richardson, A; Sakariassen, K S; Meyer, J-P; Alberts, P; Sorensen, A S

2013-03-01

This study was performed to determine the oral pharmacokinetics (PK) of EV-077 and its effects on pharmacodynamic (PD) markers. EV-077 blocks prostanoid-induced and isoprostane-induced cellular activation, and is in development for the treatment of vascular inflammation and associated complications of type-2 diabetes.. This single-ascending-dose mono-centre study was randomised, placebo-controlled, and double-blinded within each dose group. Seven EV-077 doses were administered sequentially as an oral solution: 0.0125, 0.125, 0.375, 0.75, 1.25, 1.875 and 2.5 mg/kg body weight. PK, platelet aggregation, bleeding time and safety parameters were measured. Seven to eight healthy male subjects were dosed per group: five to six subjects received EV-077 and two subjects received placebo. Tmax was reached rapidly between 0.5 h and 1.0 h. Both Cmax and AUC increased linearly with the dose. The apparent terminal half-life (t½z) increased with the dose, most likely reflecting the increasing last quantifiable concentration with increasing dose; at 2.5 mg/kg, it was 2.7-6.9 h. Measurement of platelet aggregation showed no effect at 0.0125 mg/kg, and a full and reversible inhibition at doses of 0.125-2.5 mg/kg. The average bleeding time was dose-dependently prolonged, but was always below 9 min. The PK/PD profile showed that at plasma concentrations above 20 ng/ml, EV-077 platelet aggregation was completely inhibited (>90 %). All tested doses were well tolerated. Orally administered EV-077 was well tolerated, readily absorbed, reached Cmax within 1 h, with a linear PK based on Cmax and AUC. The inhibition of platelet aggregation was complete and reversible at doses of 0.125 mg/kg and higher, and average bleeding time was below 9 min.

Dose-ranging study of the novel recombinant plasminogen activator BM 06.022 in healthy volunteers.

PubMed

Martin, U; von Möllendorff, E; Akpan, W; Kientsch-Engel, R; Kaufmann, B; Neugebauer, G

1991-10-01

The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 and protease domains of human tissue-type plasminogen activator and is unglycosylated because of its expression in Escherichia coli cells. Pharmacokinetics for activity and hemostatic effects of BM 06.022 were studied in 18 healthy male volunteers after an intravenous bolus injection over 2 minutes. BM 06.022 was administered successively at doses of 0.1125, 0.55, 2.2, 3.3, 4.4, and 5.5 MU to three volunteers. Plasma fibrinogen was unchanged; effects of BM 06.022 were observed on plasminogen only at higher doses, and dose-dependent effects were seen on alpha 2-antiplasmin and fibrin D-dimers. The concentration of plasminogen and alpha 2-antiplasmin was 87% +/- 3% and 79% +/- 3%, respectively, of baseline 2 hours after injection of 5.5 MU of BM 06.022. Fibrin D-dimers were highest with 1147 +/- 380 ng/ml at 5.5 MU of BM 06.022. The area under the activity concentration-time curve (AUC) increased dose-dependently and linearly. At 5.5 MU of BM 06.022, the AUC was 313 +/- 47 IU.hr.ml-1, the total plasma clearance was 306 +/- 40 ml/min, and the half-life was 14.4 +/- 1.1 minutes.

The linearized multistage model and the future of quantitative risk assessment.

PubMed

Crump, K S

1996-10-01

The linearized multistage (LMS) model has for over 15 years been the default dose-response model used by the U.S. Environmental Protection Agency (USEPA) and other federal and state regulatory agencies in the United States for calculating quantitative estimates of low-dose carcinogenic risks from animal data. The LMS model is in essence a flexible statistical model that can describe both linear and non-linear dose-response patterns, and that produces an upper confidence bound on the linear low-dose slope of the dose-response curve. Unlike its namesake, the Armitage-Doll multistage model, the parameters of the LMS do not correspond to actual physiological phenomena. Thus the LMS is 'biological' only to the extent that the true biological dose response is linear at low dose and that low-dose slope is reflected in the experimental data. If the true dose response is non-linear the LMS upper bound may overestimate the true risk by many orders of magnitude. However, competing low-dose extrapolation models, including those derived from 'biologically-based models' that are capable of incorporating additional biological information, have not shown evidence to date of being able to produce quantitative estimates of low-dose risks that are any more accurate than those obtained from the LMS model. Further, even if these attempts were successful, the extent to which more accurate estimates of low-dose risks in a test animal species would translate into improved estimates of human risk is questionable. Thus, it does not appear possible at present to develop a quantitative approach that would be generally applicable and that would offer significant improvements upon the crude bounding estimates of the type provided by the LMS model. Draft USEPA guidelines for cancer risk assessment incorporate an approach similar to the LMS for carcinogens having a linear mode of action. However, under these guidelines quantitative estimates of low-dose risks would not be developed for carcinogens having a non-linear mode of action; instead dose-response modelling would be used in the experimental range to calculate an LED10* (a statistical lower bound on the dose corresponding to a 10% increase in risk), and safety factors would be applied to the LED10* to determine acceptable exposure levels for humans. This approach is very similar to the one presently used by USEPA for non-carcinogens. Rather than using one approach for carcinogens believed to have a linear mode of action and a different approach for all other health effects, it is suggested herein that it would be more appropriate to use an approach conceptually similar to the 'LED10*-safety factor' approach for all health effects, and not to routinely develop quantitative risk estimates from animal data.

Fractionated irradiation of carbon beam and the isoeffect dose on acute reaction of skin

PubMed Central

Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Koda, Kana; Koike, Sachiko; Ando, Koichi; Furusawa, Yoshiya

2014-01-01

Purpose: The aim of this study was to clear any specific LETs cause change in skin reaction. We irradiated mice feet with mono-energetic and SOBP carbon ions, to obtain dose–response of early skin reaction at different LETs. Materials and methods: Mice: C3H/HeMsNrsf female mice aged 4 months old were used for this study. The animals were produced and maintained in specific pathogen-free (SPF) facilities. Irradiation: The mice right hind legs received daily fractionated irradiation ranged from single to six fractions. Carbon ions (12C6+) were accelerated by the HIMAC synchrotron to 290 MeV/u. Irradiation was conducted using horizontal carbon-ion beams with a dose rate of ∼3 Gy/min. We chose the LETs at entrance of plateau (20keV/μm) and the SOBP (proximal: 40 keV/μm, middle: 45 keV/μm, distal: 60 keV/μm, distal-end: 80 keV/μm). The reference beam was 137Cs gamma rays with a dose rate of 1.2 Gy/min. Skin reaction: Skin reaction of the irradiated legs was scored every other day, between the14th and 35th post-irradiation days. Our scoring scale consisted of seven steps, ranging from 0.5 to 3.5 [ 1]. The skin score analyzed a result by the method that described by Ando et al. [ 2]. The Fe-plot proposed by Douglas and Fowler was used as a multifraction linear quadratic model. A plot between the reciprocal of the isoeffect dose and the dose per fraction resulted in a straight line. Results: Required isoeffect total dose increased linearly with the fraction numbers on a semi-logarithmic chart at LET 20–60 keV/µm SOBP beam. The isoeffect total dose decreased with the increase in the LET. However, no increases in isoeffect total dose were observed at few fractionations at 80 keV/µm. (data not shown) Using an Fe-plot, we analyzed the isoeffect total dose to evaluate the dependence on Carbon beam, or gamma ray. When I irradiate it by gamma ray, an Fe-plot shows linearly. But, irradiated by Carbon beam, an Fe-plot bent at low fractions (Fig. 1). Conclusion: The LQ-model-based Fe-plot could not fit skin reaction at few fractions at high-LET. Clinical Trial Registration number if required: No.Fig. 1.The reciprocal of the isoeffect dose is plotted against the dose per fraction. (i) Gamma ray: Fe-plot was linear. (ii) C-ions: Fe-plot bent at low fractions.

Characterization of Al2O3 optically stimulated luminescence films for 2D dosimetry using a 6 MV photon beam

NASA Astrophysics Data System (ADS)

Ahmed, M. F.; Shrestha, N.; Schnell, E.; Ahmad, S.; Akselrod, M. S.; Yukihara, E. G.

2016-11-01

This work evaluates the dosimetric properties of newly developed optically stimulated luminescence (OSL) films, fabricated with either Al2O3:C or Al2O3:C,Mg, using a prototype laser scanning reader, a developed image reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing OSL films (Al2O3:C and Al2O3:C,Mg) and a radiochromic film (Gafchromic EBT3) were irradiated using a 6 MV photon beam using different doses, field sizes, with and without wedge filter. Dependence on film orientation of the OSL system was also tested. Diode-array (MapCHECK) and ionization chamber measurements were performed for comparison. The OSLD film doses agreed with the MapCHECK and ionization chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system background and minimum detectable dose (MDD) were  <0.5 mGy, and the dose response was approximately linear from the MDD up to a few grays (the linearity correction was  <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose profiles agreed with those obtained using EBT3 films (analyzed using the triple channel method) in the high dose regions of the images. In the low dose regions, the dose profiles from the OSLD films were more reproducible than those from the EBT3 films. We also demonstrated that the OSL film data are independent on scan orientation and field size over the investigated range. The results demonstrate the potential of OSLD films for 2D dosimetry, particularly for the characterization of small fields, due to their wide dynamic range, linear response, resolution and dosimetric properties. The negligible background and potential simple calibration make these OSLD films suitable for remote audits. The characterization presented here may motivate further commercial development of a 2D dosimetry system based on the OSL from Al2O3:C or Al2O3:C,Mg.

Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

PubMed

Zhao, R; Wang, H; Wang, X; Feng, F

2017-03-01

This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09-1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p non-linear  < 0.001 and p non-linear  = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI -0.03 to 0.06, p = 0.582). SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Estimation of absorbed dose in clinical radiotherapy linear accelerator beams: Effect of ion chamber calibration and long-term stability

PubMed Central

Ravichandran, Ramamoorthy; Binukumar, Johnson Pichy; Davis, Cheriyathmanjiyil Antony

2013-01-01

The measured dose in water at reference point in phantom is a primary parameter for planning the treatment monitor units (MU); both in conventional and intensity modulated/image guided treatments. Traceability of dose accuracy therefore still depends mainly on the calibration factor of the ion chamber/dosimeter provided by the accredited Secondary Standard Dosimetry Laboratories (SSDLs), under International Atomic Energy Agency (IAEA) network of laboratories. The data related to Nd,water calibrations, thermoluminescent dosimetry (TLD) postal dose validation, inter-comparison of different dosimeter/electrometers, and validity of Nd,water calibrations obtained from different calibration laboratories were analyzed to find out the extent of accuracy achievable. Nd,w factors in Gray/Coulomb calibrated at IBA, GmBH, Germany showed a mean variation of about 0.2% increase per year in three Farmer chambers, in three subsequent calibrations. Another ion chamber calibrated in different accredited laboratory (PTW, Germany) showed consistent Nd,w for 9 years period. The Strontium-90 beta check source response indicated long-term stability of the ion chambers within 1% for three chambers. Results of IAEA postal TL “dose intercomparison” for three photon beams, 6 MV (two) and 15 MV (one), agreed well within our reported doses, with mean deviation of 0.03% (SD 0.87%) (n = 9). All the chamber/electrometer calibrated by a single SSDL realized absorbed doses in water within 0.13% standard deviations. However, about 1-2% differences in absorbed dose estimates observed when dosimeters calibrated from different calibration laboratories are compared in solid phantoms. Our data therefore imply that the dosimetry level maintained for clinical use of linear accelerator photon beams are within recommended levels of accuracy, and uncertainties are within reported values. PMID:24672156

Dose dependency of time of onset of radiation-induced growth hormone deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clayton, P.E.; Shalet, S.M.

1991-02-01

Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showedmore » that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.« less

Dose-dependent establishment of Trichuris suis larvae in Göttingen minipigs.

PubMed

Vejzagić, Nermina; Roepstorff, Allan; Kringel, Helene; Thamsborg, Stig Milan; Nielsen, Mads Pårup; Kapel, Christian M O

2015-03-15

Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO. Copyright © 2015 Elsevier B.V. All rights reserved.

Population pharmacokinetics of levofloxacin in Korean patients.

PubMed

Kiem, Sungmin; Ryu, Sung-Mun; Lee, Yun-Mi; Schentag, Jerome J; Kim, Yang-Wook; Kim, Hyeon-Kuk; Jang, Hang-Jae; Joo, Yong-Don; Jin, Kyubok; Shin, Jae-Gook; Ghim, Jong-Lyul

2016-08-01

Levofloxacin (LVFX) has different effects depending on the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio. While AUC can be expressed as dose/clearance (CL), we measured serial concentrations of LVFX in Koreans and tried to set a Korean-specific equation, estimating the CL of the antibiotic. In total, 38 patients, aged 18-87 years, received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on their renal function. Four plasma samples were obtained according to a D optimal sampling design. The population pharmacokinetic (PK) parameters of LVFX were estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 ×  (CLCR/75)(1.32). The CL of LVFX in Koreans is expected to be lower than that in Western people.

Glucosamine for the Treatment of Osteoarthritis: The Time Has Come for Higher-Dose Trials.

PubMed

McCarty, Mark F; O'Keefe, James H; DiNicolantonio, James J

2018-04-18

Although clinical trials with glucosamine in osteoarthritis have yielded mixed results, leading to doubts about its efficacy, the utility of glucosamine for preventing joint destruction and inflammation is well documented in rodent models of arthritis, including models of spontaneous osteoarthritis. The benefit of oral glucosamine in adjuvant arthritis is markedly dose dependent, likely reflecting a modulation of tissue levels of UDP-N-acetylglucosamine that in turn influences mucopolysaccharide synthesis and the extent of protein O-GlcNAcylation. Importantly, the minimal oral dose of glucosamine that exerts a detectible benefit in adjuvant arthritis achieves plasma glucosamine levels similar to those achieved when the standard clinical dose of glucosamine, 1.5 g daily, is administered as a bolus. The response of plasma glucosamine levels to an increase in glucosamine intake is nearly linear. Remarkably, every published clinical trial with glucosamine has employed the same 1.5 g dose that Rottapharm recommended for its proprietary glucosamine sulfate product decades ago, yet there has never been any published evidence that this dose is optimal with respect to efficacy and side effects. If this dose is on the edge of demonstrable clinical efficacy when experimental design is ideal, then variations in the patient populations targeted, the assessment vehicles employed, and the potency of glucosamine preparations tested could be expected to yield some null results. Failure to employ bolus dosing may also be a factor in the null results observed in the GAIT study and other trials. Clinical studies evaluating the dose dependency of glucosamine's influence on osteoarthritis are long overdue.

A distributed lag approach to fitting non-linear dose-response models in particulate matter air pollution time series investigations.

PubMed

Roberts, Steven; Martin, Michael A

2007-06-01

The majority of studies that have investigated the relationship between particulate matter (PM) air pollution and mortality have assumed a linear dose-response relationship and have used either a single-day's PM or a 2- or 3-day moving average of PM as the measure of PM exposure. Both of these modeling choices have come under scrutiny in the literature, the linear assumption because it does not allow for non-linearities in the dose-response relationship, and the use of the single- or multi-day moving average PM measure because it does not allow for differential PM-mortality effects spread over time. These two problems have been dealt with on a piecemeal basis with non-linear dose-response models used in some studies and distributed lag models (DLMs) used in others. In this paper, we propose a method for investigating the shape of the PM-mortality dose-response relationship that combines a non-linear dose-response model with a DLM. This combined model will be shown to produce satisfactory estimates of the PM-mortality dose-response relationship in situations where non-linear dose response models and DLMs alone do not; that is, the combined model did not systemically underestimate or overestimate the effect of PM on mortality. The combined model is applied to ten cities in the US and a pooled dose-response model formed. When fitted with a change-point value of 60 microg/m(3), the pooled model provides evidence for a positive association between PM and mortality. The combined model produced larger estimates for the effect of PM on mortality than when using a non-linear dose-response model or a DLM in isolation. For the combined model, the estimated percentage increase in mortality for PM concentrations of 25 and 75 microg/m(3) were 3.3% and 5.4%, respectively. In contrast, the corresponding values from a DLM used in isolation were 1.2% and 3.5%, respectively.

A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

PubMed

Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-25

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT. © The Author 2015. Published by Oxford University Press on behalf of CINP.

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

PubMed Central

Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong

2015-01-01

Background: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Methods: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Results: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. Conclusions: We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT. PMID:25716777

Characterisation of a plastic scintillation detector to be used in a multicentre stereotactic radiosurgery dosimetry audit

NASA Astrophysics Data System (ADS)

Dimitriadis, A.; Patallo, I. Silvestre; Billas, I.; Duane, S.; Nisbet, A.; Clark, C. H.

2017-11-01

Scintillation detectors are considered highly suitable for dosimetric measurement of small fields in radiotherapy due to their near-tissue equivalence and their small size. A commercially available scintillation detector, the Exradin W1 (Standard Imaging, Middleton, USA), has been previously characterised by two independent studies (Beierholm et al., 2014; Carrasco et al., 2015a, 2015b) but the results from these publications differed in some aspects (e.g. energy dependence, long term stability). The respective authors highlighted the need for more studies to be published (Beierholm et al., 2015; Carrasco et al., 2015a, 2015b). In this work, the Exradin W1 was characterised in terms of dose response, dependence on dose rate, energy, temperature and angle of irradiation, and long-term stability. The observed dose linearity, short-term repeatability and temperature dependence were in good agreement with previously published data. Appropriate corrections should therefore be applied, where possible, in order to achieve measurements with low-uncertainty. The angular dependence was characterised along both the symmetrical and polar axis of the detector for the first time in this work and a dose variation of up to 1% was observed. The response of the detector was observed to decrease at a rate of approximately 1.6% kGy-1 for the first 5 kGy delivered, and then stabilised to 0.2% kGy-1 in the subsequent 20 kGy. The main goal of this work was to assess the suitability of the Exradin W1 for use in dose verification measurements for stereotactic radiosurgery. The results obtained confirm that the detector is suitable for use in such situations. The detector is now utilised in a multi-centre stereotactic radiosurgery dosimetric audit, with the application of appropriate correction factors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stelljes, T. S., E-mail: tenzin.s.stelljes@uni-oldenburg.de; Looe, H. K.; Chofor, N.

Purpose: The dosimetric properties of the OCTAVIUS Detector 1500 (OD1500) ionization chamber array (PTW-Freiburg, Freiburg, Germany) have been investigated. A comparative study was carried out with the OCTAVIUS Detector 729 and OCTAVIUS Detector 1000 SRS arrays. Methods: The OD1500 array is an air vented ionization chamber array with 1405 detectors in a 27 × 27 cm{sup 2} measurement area arranged in a checkerboard pattern with a chamber-to-chamber distance of 10 mm in each row. A sampling step width of 5 mm can be achieved by merging two measurements shifted by 5 mm, thus fulfilling the Nyquist theorem for intensity modulatedmore » dose distributions. The stability, linearity, and dose per pulse dependence were investigated using a Semiflex 31013 chamber (PTW-Freiburg, Freiburg, Germany) as a reference detector. The effective depth of measurement was determined by measuring TPR curves with the array and a Roos chamber type 31004 (PTW-Freiburg, Freiburg, Germany). Comparative output factor measurements were performed with the array, the Semiflex 31010 ionization chamber and the Diode 60012 (both PTW-Freiburg, Freiburg, Germany). The energy dependence of the OD1500 was measured by comparing the array’s readings to those of a Semiflex 31010 ionization chamber for varying mean photon energies at the depth of measurement, applying to the Semiflex chamber readings the correction factor k{sub NR} for nonreference conditions. The Gaussian lateral dose response function of a single array detector was determined by searching the convolution kernel suitable to convert the slit beam profiles measured with a Diode 60012 into those measured with the array’s central chamber. An intensity modulated dose distribution measured with the array was verified by comparing a OD1500 measurement to TPS calculations and film measurements. Results: The stability and interchamber sensitivity variation of the OD1500 array were within ±0.2% and ±0.58%, respectively. Dose linearity was within 1% over the range from 5 to 1000 MU. The effective point of measurement of the OD1500 for dose measurements in RW3 phantoms was determined to be (8.7 ± 0.2) mm below its front surface. Output factors showed deviations below 1% for field sizes exceeding 4 × 4 cm{sup 2}. The dose per pulse dependence was smaller than 0.4% for doses per pulse from 0.2 to 1 mGy. The energy dependence of the array did not exceed ±0.9%. The parameter σ of the Gaussian lateral dose response function was determined as σ{sub 6MV} = (2.07 ± 0.02) mm for 6 MV and σ{sub 15MV} = (2.09 ± 0.02) mm for 15 MV. An IMRT verification showed passing rates well above 90% for a local 3 mm/3% criterion. Conclusions: The OD1500 array’s dosimetric properties showed the applicability of the array for clinical dosimetry with the possibility to increase the spatial sampling frequency and the coverage of a dose distribution with the sensitive areas of ionization chambers by merging two measurements.« less

Effects of isobutyrate supplementation on ruminal microflora, rumen enzyme activities and methane emissions in Simmental steers.

PubMed

Wang, C; Liu, Q; Zhang, Y L; Pei, C X; Zhang, S L; Wang, Y X; Yang, W Z; Bai, Y S; Shi, Z G; Liu, X N

2015-02-01

The objective of this study was to evaluate the effects of isobutyrate supplementation on rumen microflora, enzyme activities and methane emissions in Simmental steers consuming a corn stover-based diet. Eight ruminally cannulated Simmental steers were used in a replicated 4 × 4 Latin square experiment. The treatments were control (without isobutyrate), low isobutyrate (LIB), moderate isobutyrate (MIB) and high isobutyrate (HIB) with 8.4, 16.8 and 25.2 g isobutyrate per steer per day respectively. Isobutyrate was hand-mixed into the concentrate portion. Diet consisted of 60% corn stover and 40% concentrate [dry matter (DM) basis]. Dry matter intake (averaged 9 kg/day) was restricted to a maximum of 90% of ad libitum intake. Population of total bacteria, cellulolytic bacteria and anaerobic fungi were linearly increased, whereas that of protozoa and total methanogens was linearly reduced with increasing isobutyrate supplementation. Real-time PCR quantification of population of Ruminococcus albus, Ruminococcus flavefaciens, Butyrivibrio fibrisolvens and Fibrobacter succinogenes was linearly increased with increasing isobutyrate supplementation. Activities of carboxymethyl cellulase, xylanase and β-glucosidase were linearly increased, whereas that of protease was linearly reduced. Methane production was linearly decreased with increasing isobutyrate supplementation. Effective degradabilities of cellulose and hemicellulose of corn stover were linearly increased, whereas that of crude protein in diet was linearly decreased with increasing isobutyrate supplementation. The present results indicate that isobutyrate supplemented improved microflora, rumen enzyme activities and methane emissions in steers. It was suggested that the isobutyrate stimulated the digestive micro-organisms or enzymes in a dose-dependent manner. In the experimental conditions of this trial, the optimum isobutyrate dose was approximately 16.8 g isobutyrate per steer per day. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

A multiscale filter for noise reduction of low-dose cone beam projections

NASA Astrophysics Data System (ADS)

Yao, Weiguang; Farr, Jonathan B.

2015-08-01

The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, \\text{exp}≤ft(-{{x}2}/2σ f2\\right) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of {σf} , which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ f2 is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

Radiotherapy Dose Fractionation under Parameter Uncertainty

NASA Astrophysics Data System (ADS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-11-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

Evaluation of a lithium formate EPR dosimetry system for dose measurements around {sup 192}Ir brachytherapy sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antonovic, Laura; Gustafsson, Haakan; Alm Carlsson, Gudrun

2009-06-15

A dosimetry system using lithium formate monohydrate (HCO{sub 2}Li{center_dot}H{sub 2}O) as detector material and electron paramagnetic resonance (EPR) spectroscopy for readout has been used to measure absorbed dose distributions around clinical {sup 192}Ir sources. Cylindrical tablets with diameter of 4.5 mm, height of 4.8 mm, and density of 1.26 g/cm{sup 3} were manufactured. Homogeneity test and calibration of the dosimeters were performed in a 6 MV photon beam. {sup 192}Ir irradiations were performed in a PMMA phantom using two different source models, the GammaMed Plus HDR and the microSelectron PDR-v1 model. Measured absorbed doses to water in the PMMA phantommore » were converted to the corresponding absorbed doses to water in water phantoms of dimensions used by the treatment planning systems (TPSs) using correction factors explicitly derived for this experiment. Experimentally determined absorbed doses agreed with the absorbed doses to water calculated by the TPS to within {+-}2.9%. Relative standard uncertainties in the experimentally determined absorbed doses were estimated to be within the range of 1.7%-1.3% depending on the radial distance from the source, the type of source (HDR or PDR), and the particular absorbed doses used. This work shows that a lithium formate dosimetry system is well suited for measurements of absorbed dose to water around clinical HDR and PDR {sup 192}Ir sources. Being less energy dependent than the commonly used thermoluminescent lithium fluoride (LiF) dosimeters, lithium formate monohydrate dosimeters are well suited to measure absorbed doses in situations where the energy dependence cannot easily be accounted for such as in multiple-source irradiations to verify treatment plans. Their wide dynamic range and linear dose response over the dose interval of 0.2-1000 Gy make them suitable for measurements on sources of the strengths used in clinical applications. The dosimeter size needs, however, to be reduced for application to single-source dosimetry.« less

ESR response of phenol compounds for dosimetry of gamma photon beams

NASA Astrophysics Data System (ADS)

Marrale, M.; Longo, A.; Panzeca, S.; Gallo, S.; Principato, F.; Tomarchio, E.; Parlato, A.; Buttafava, A.; Dondi, D.; Zeffiro, A.

2014-11-01

In the present paper we investigate the features of IRGANOX® 1076 phenols as a material for electron spin resonance (ESR) dosimetry. We experimentally analyzed the ESR response of pellets of IRGANOX® 1076 phenols irradiated with 60Co photons. The best experimental parameters (modulation amplitude and microwave power) for dosimetric applications have been obtained. The dependence of ESR signal as function of γ dose is found to be linear in the dose range studied (12-60 Gy) and the lowest measurable dose is found to be of the order of 1 Gy. The signal after irradiation is very stable in the first thirty days. From the point of view of the tissue equivalence, these materials have mass energy absorption coefficient values comparable with those of soft tissue.

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, Kerry; Cucinotta, Francis A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

NASA Technical Reports Server (NTRS)

Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

2014-01-01

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zasneda, Sabriani; Widita, Rena

2010-06-22

Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometricalmore » factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.« less

Comparison between DCA - SSO - VDR and VMAT dose delivery techniques for 15 SRS/SRT patients

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.

2018-02-01

To evaluate dose delivery between Dynamic Conformal Arc (DCA) - Segment Shape Optimization (SSO) - Variation Dose Rate (VDR) and Volumetric Modulated Arc Therapy (VMAT) techniques for fifteen SRS patients using Versa HD® lineer accelerator. Fifteen SRS / SRT patient's optimum treatment planning were performed using Monaco5.11® treatment planning system (TPS) with 1 coplanar and 3 non-coplanar fields for VMAT technique, then the plans were reoptimized with the same optimization parameters for DCA - SSO - VDR technique. The advantage of DCA - SSO - VDR technique were determined less MUs and beam on time, also larger segments decrease dosimetric uncertainities of small fields quality assurance. The advantage of VMAT technique were determined a little better GI, CI, PCI, brain V12Gy and brain mean dose. The results show that the clinical objectives and plans for both techniques satisfied all organs at risks (OARs) dose constraints. Depends on the shape and localization of target, we could choose one of these techniques for linear accelerator based SRS / SRT treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battum, LJ van; Heukelom, S

Purpose This study investigates the origin of lateral optical density (OD) variation for Gafchromic film (EBT and EBT2) scanned in transmission mode with Epson flatbed scanners (1680 Expression Pro and 10000XL). Effects investigated are: cross talk, optical path length and polarization. Methods Cross talk has been examined with triangular shaped light-transmission sheets with OD ranging from 0 to opaque. Optical path length has been studied with absorptive and reflective OD-filters (OD range 0.2 to 2.0). Dependency on light-polarization on the scanner read out has been investigated using linear polarizer sheets. All experiments have been performed at centre scanner position (normmore » point) and at several lateral scan positions, without and with (un)irradiated EBT-film. Dose values used ranged between 0.2 to 9 Gy, yielding an OD-range between 0.25 to 1.1. Results The lateral OD variation is dose dependent and increases up to 14% at most lateral position for dose up to 9 Gy. Cross talk effect contributes to 0.5% in clinical used OD ranges but equals 2% for extreme high dose gradients. Film induced optical path length will effect the lateral OD variation up to 3% at most lateral points. Light polarization is inherent present in these scanners due to multiple reflection on mirrors. In addition film induced polarization is the most important effect generating the observed lateral OD variation. Both Gafchromic film base and sensitive layer have polarizing capabilities; for the sensitive layer its influence is dose dependent. Conclusions Lateral OD variation origins from optical physics (i.e. polarization and reflection) related to scanner and film construction. Cross talk can be ignored in film dosimetry for clinical used dose values and gradients. Therefore it is recommended to determine the lateral OD variation per film type and scanner.« less

Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.

Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thicknessmore » between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.« less

Verification of intensity modulated profiles using a pixel segmented liquid-filled linear array.

PubMed

Pardo, J; Roselló, J V; Sánchez-Doblado, F; Gómez, F

2006-06-07

A liquid isooctane (C8H18) filled ionization chamber linear array developed for radiotherapy quality assurance, consisting of 128 pixels (each of them with a 1.7 mm pitch), has been used to acquire profiles of several intensity modulated fields. The results were compared with film measurements using the gamma test. The comparisons show a very good matching, even in high gradient dose regions. The volume-averaging effect of the pixels is negligible and the spatial resolution is enough to verify these regions. However, some mismatches between the detectors have been found in regions where low-energy scattered photons significantly contribute to the total dose. These differences are not very important (in fact, the measurements of both detectors are in agreement using the gamma test with tolerances of 3% and 3 mm in most of those regions), and may be associated with the film energy dependence. In addition, the linear array repeatability (0.27% one standard deviation) is much better than the film one ( approximately 3%). The good repeatability, small pixel size and high spatial resolution make the detector ideal for the real time profile verification of high gradient beam profiles like those present in intensity modulated radiation therapy and radiosurgery.

Effects of Lactobacillus acidophilus supplementation on growth performance, nutrient digestibility, fecal microbial and noxious gas emission in weaning pigs.

PubMed

Lan, Ruixia; Koo, Jinmo; Kim, Inho

2017-03-01

Antibiotics used as growth promoters in livestock have been banned in the European Union since 2006. Antibiotics alternatives have focused on probiotics, such as Lactobacillus acidophilus. The concentration of L. acidophilus is considered crucial for obtaining the desired effects. However, limited studies have been conducted to test the dose-dependent effects of L. acidophilus. Therefore, the present study aimed to test the dose-dependent effects of L. acidophilus on growth performance, nutrient digestibility, fecal microbial flora and fecal noxious gas emission in weaning pigs. Lactobacillus acidophilus supplementation increased (P < 0.05) average daily gain, average daily feed intake, apparent nutrient digestibility of dry matter, nitrogen and gross energy, and Lactobacillus counts compared to the basal diet treatment, and a linear effect (P < 0.05) was observed on those criteria. Escherichia coli counts and NH 3 emission were decreased (P < 0.05) by L. acidophilus supplementation, and a linear effect (P < 0.05) was observed on E. coli counts. These results suggest that L. acidophilus could be used as an antibiotic alternative by improving growth performance, nutrient digestibility and gut balance (i.e. increased Lactobacillus counts and decreased E. coli counts), and decreasing NH3 emission, of weaning pigs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Analytical studies into radiation-induced starch damage in black and white peppers

NASA Astrophysics Data System (ADS)

Sharif, M. M.; Farkas, J.

1993-07-01

Temperature dependency of the apparent viscosity of heat-gelatinized suspensions of untreated and irradiated pepper samples has been investigated. There was a close linear correlation between the logaritm of "fluidity" /reciprocal of the apparent viscosity) and the reciprocal absolute temperature of the measurement. The slope of the regression line(the temperature dependence of fluidity) increased with the radiation dose. Gelatinization thermograms of aqueous suspensions of ground pepper samples were obtained by differential scanning calorimetry. Temperature characteristics of heat-gelatinization endotherms showed no significant differences between untreated and irradiated samples. A colorimetric method for damaged starch, the estimation of reducing power, and the alcohol-induced turbidity of aqueous extracts showed statistically significant increases of starch damage at doses higher than 4 kGy. These indices of starch-depolymerization have been changed less dramatically by irradiation than the apparent viscosity of the heat-gelatinized suspensions.

Clinical application of the OneDose™ Patient Dosimetry System for total body irradiation

NASA Astrophysics Data System (ADS)

Best, S.; Ralston, A.; Suchowerska, N.

2005-12-01

The OneDose™ Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose™ dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose™ patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Linear response of mutans streptococci to increasing frequency of xylitol chewing gum use: a randomized controlled trial [ISRCTN43479664

PubMed Central

Ly, Kiet A; Milgrom, Peter; Roberts, Marilyn C; Yamaguchi, David K; Rothen, Marilynn; Mueller, Greg

2006-01-01

Background Xylitol is a naturally occurring sugar substitute that has been shown to reduce the level of mutans streptococci in plaque and saliva and to reduce tooth decay. It has been suggested that the degree of reduction is dependent on both the amount and the frequency of xylitol consumption. For xylitol to be successfully and cost-effectively used in public health prevention strategies dosing and frequency guidelines should be established. This study determined the reduction in mutans streptococci levels in plaque and unstimulated saliva to increasing frequency of xylitol gum use at a fixed total daily dose of 10.32 g over five weeks. Methods Participants (n = 132) were randomized to either active groups (10.32 g xylitol/day) or a placebo control (9.828 g sorbitol and 0.7 g maltitol/day). All groups chewed 12 pieces of gum per day. The control group chewed 4 times/day and active groups chewed xylitol gum at a frequency of 2 times/day, 3 times/day, or 4 times/day. The 12 gum pieces were evenly divided into the frequency assigned to each group. Plaque and unstimulated saliva samples were taken at baseline and five-weeks and were cultured on modified Mitis Salivarius agar for mutans streptococci enumeration. Results There were no significant differences in mutans streptococci level among the groups at baseline. At five-weeks, mutans streptococci levels in plaque and unstimulated saliva showed a linear reduction with increasing frequency of xylitol chewing gum use at the constant daily dose. Although the difference observed for the group that chewed xylitol 2 times/day was consistent with the linear model, the difference was not significant. Conclusion There was a linear reduction in mutans streptococci levels in plaque and saliva with increasing frequency of xylitol gum use at a constant daily dose. Reduction at a consumption frequency of 2 times per day was small and consistent with the linear-response line but was not statistically significant. PMID:16556326

SU-E-I-49: The Evaluation of Usability of Multileaf Collimator for Diagnostic Radiation in Cephalometric Exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, S; Kim, K; Jung, H

Purpose: This study evaluated usability of Multileaf collimator (MLC) for diagnostic radiation in cephalometric exposure using optical stimulated luminance dosimeters (OSLDs) Methods: The MLC material was made alloy tool steel (SKD-11) and the density of it is 7.89g/m3 that is similar to it of steel (Fe, 7.85 g/m3) and the MLC was attached to general radiography unit (Rex-650R, Listem Inc, Korea) for cephalometric exposure. The OSLDs that used were nanoDotTM Dosimeter (Landauer Inc, Glenwood, USA) and we read out OSLDs with micro star system (Landauer Inc, Glenwood, USA). The Optical annealing system contained fluorescent lamps (Osram lumilux, 24 W, 280more » ∼780 nm). To measure absorbed dose using OSLDs, was carried out dosimetric characteristics of OSLDs. Based on these, we evaluated dose reduction of critical organ (Eyes, Thyroids) with MLC in cephalometric exposure Results: The dosimetric characteristics were following that batch homogeneity was 1.21% and reproducibility was 0.96% of the coefficient of variation The linearity was that the correlation of between dose and count was fitted by linear function (dose,mGy = 0.00029 × Count, R2 =0.997). The range of angular dependence was from −3.6% to 3.7% variation when each degree was normalized by zero degree. The organ dose of Rt. eye, Lt eye, thyroids were 77.8 μGy, 337.0 μGy, 323.1μGy, respectively in open field and the dose reduction of organ dose was 10.6%(8.3μGy), 12.4 %(42 μGy), 87.1%(281.4μGy) with MLC Conclusion: We certified dose reduction of organ dose in cephalometric exposure. The dose reduction of Eye was 11% because of reduction of field size and it of thyroids was 87% by primary beam shielding.« less

Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.

PubMed

Guttenplan, J B; Milstein, S

1982-01-01

Salmonella tester strains which are reverted by base-pair substitution mutagens are relatively insensitive to the mutagenic effects of N-methyl-N-nitroso compounds. One reason for this insensitivity is the ability of these strains to withstand low doses of these compounds before they become sensitive to their mutagenic effects. In this report it is shown that mutagenesis induced by treatment of Salmonella typhimurium TA 1535 with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) in buffer is biphasic with a low sensitivity range at low doses where little mutagenesis occurs, followed by a high sensitivity range whose onset begins after an apparent threshold dose has been exceeded. levels of O6-methylguanine (O6-MeG) in the DNA extracted from the bacteria follow a similar dose-response curve suggesting a dependency of mutagenesis on O6-MeG. In contrast, levels of 7-methylguanine (7-MeG) in the DNA increase linearly with dose. O6-MeG was undetectable at the lowest dose of MNNG whereas 7-MeG was readily detectable. Although such resistance to O6-alkylation has been demonstrated in MNNG- pretreated (adapted) E. coli, it has not been reported in unpretreated cells. Then isolated DNA was treated with MNNG a linear dose-response in the generation of O6-MeG was observed. The lack of O6-MeG in DNA isolated from MNNG treated cells after low doses is attributed to a saturable, constitutive repair activity in the bacteria. An attempt to observe the removal of O6-MeG from the bacteria after exposure to a short challenge dose of N-nitroso-N-methylurea (NMU) followed by a subsequent incubation in buffer was unsuccessful, probably because all the repair occurred within the time necessary to treat and lyse the cells.

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

PubMed

Zahnreich, Sebastian; Ebersberger, Anne; Kaina, Bernd; Schmidberger, Heinz

2015-04-01

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.

Comparison of cellular lethality in DNA repair-proficient or -deficient cell lines resulting from exposure to 70 MeV/n protons or 290 MeV/n carbon ions.

PubMed

Genet, Stefan C; Maeda, Junko; Fujisawa, Hiroshi; Yurkon, Charles R; Fujii, Yoshihiro; Romero, Ashley M; Genik, Paula C; Fujimori, Akira; Kitamura, Hisashi; Kato, Takamitsu A

2012-11-01

Charged particle therapy utilizing protons or carbon ions has been rapidly intensifying over recent years. The present study was designed to jointly investigate these two charged particle treatment modalities with respect to modeled anatomical depth-dependent dose and linear energy transfer (LET) deliveries to cells with either normal or compromised DNA repair phenotypes. We compared cellular lethality in response to dose, LET and Bragg peak location for accelerated protons and carbon ions at 70 and 290 MeV/n, respectively. A novel experimental live cell irradiation OptiCell™ in vitro culture system using three different Chinese hamster ovary (CHO) cells as a mammalian model was conducted. A wild-type DNA repair-competent CHO cell line (CHO 10B2) was compared to two other CHO cell lines (51D1 and xrs5), each genetically deficient with respect to one of the two major DNA repair pathways (homologous recombination and non-homologous end joining pathways, respectively) following genotoxic insults. We found that wild-type and homologous recombination-deficient (Rad51D) cellular lethality was dependent on both the dose and LET of the carbon ions, whereas it was only dependent on dose for protons. The non-homologous end joining deficient cell line (Ku80 mutant) showed nearly identical dose-response profiles for both carbon ions and protons. Our results show that the increasingly used modality of carbon ions as charged particle therapy is advantageous to protons in a radiotherapeutic context, primarily for tumor cells proficient in non-homologous end joining DNA repair where cellular lethality is dependent not only on the dose as in the case of more common photon therapeutic modalities, but more importantly on the carbon ion LETs. Genetic characterization of patient tumors would be key to individualize and optimize the selection of radiation modality, clinical outcome and treatment cost.

Assessment of human exposure doses received by activation of medical linear accelerator components

NASA Astrophysics Data System (ADS)

Lee, D.-Y.; Kim, J.-H.; Park, E.-T.

2017-08-01

This study analyzes the radiation exposure dose that an operator can receive from radioactive components during maintenance or repair of a linear accelerator. This study further aims to evaluate radiological safety. Simulations are performed on 10 MV and 15 MV photon beams, which are the most frequently used high-energy beams in clinics. The simulation analyzes components in order of activity and the human exposure dose based on the amount of neutrons received. As a result, the neutron dose, radiation dose, and human exposure dose are ranked in order of target, primary collimator, flattening filter, multi-leaf collimator, and secondary collimator, where the minimum dose is 9.34E-07 mSv/h and the maximum is 1.71E-02 mSv/h. When applying the general dose limit (radiation worker 20 mSv/year, pubic 1 mSv/year) in accordance with the Nuclear Safety Act, all components of a linear accelerator are evaluated as below the threshold value. Therefore, the results suggest that there is no serious safety issue for operators in maintaining and repairing a linear accelerator. Nevertheless, if an operator recognizes an exposure from the components of a linear accelerator during operation and considers the operating time and shielding against external exposure, exposure of the operator is expected to be minimized.

SU-E-T-385: 4D Radiobiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fourkal, E; Hossain, M; Veltchev, I

2014-06-01

Purpose: The linear-quadratic model is the most prevalent model for planning dose fractionation in radiation therapy in the low dose per fraction regimens. However for high-dose fractions, used in SRS/SBRT/HDR treatments the LQ model does not yield accurate predictions, due to neglecting the reduction in the number of sublethal lesions as a result of their conversion to lethal lesions with subsequent irradiation. Proper accounting for this reduction in the number of sublethally damaged lesions leads to the dependence of the survival fraction on the temporal structure of the dose. The main objective of this work is to show that themore » functional dependence of the dose rate on time in each voxel is an important additional factor that can significantly influence the TCP. Methods: Two SBRT lung plans have been used to calculate the TCPs for the same patient. One plan is a 3D conformal plan and the other is an IMRT plan. Both plans are normalized so that 99.5% of PTV volume receives the same prescription dose of 50 Gy in 5 fractions. The dose rate in each individual voxel is calculated as a function of treatment time and subsequently used in the calculation of TCP. Results: The calculated TCPs show that shorter delivery times lead to greater TCP, despite all delivery times being short compared to the repair half-time for sublethal lesions. Furthermore, calculated TCP(IMRT) =0.308 for the IMRT plan is smaller than TCP(3D) =0.425 for 3D conformal, even though it shows greater tumor hot spots and equal PTV coverage. The calculated TCPs are considerably lower compared to those based on the LQ model for which TCP=1 for both plans. Conclusion: The functional dependence of the voxel-by-voxel dose rate on time may be an important factor in predicting the treatment outcome and cannot be neglected in radiobiological modeling.« less

Dose response relationship in anti-stress gene regulatory networks.

PubMed

Zhang, Qiang; Andersen, Melvin E

2007-03-02

To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on the level of local gains, presence of gain-changing events, and degree of feedforward gene activation, this region can appear as superlinear, sublinear, or even J-shaped. The general dose response transition proposed here was further examined in a complex anti-electrophilic stress pathway, which involves multiple genes, enzymes, and metabolic reactions. This work would help biologists and especially toxicologists to better assess and predict the cellular impact brought about by biological stressors.

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

PubMed

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.

Method for simulating dose reduction in digital mammography using the Anscombe transformation.

PubMed

Borges, Lucas R; Oliveira, Helder C R de; Nunes, Polyana F; Bakic, Predrag R; Maidment, Andrew D A; Vieira, Marcelo A C

2016-06-01

This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-11-08

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

PubMed Central

Millar, W T; Davidson, S E

2013-01-01

Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. Results: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence. Conclusion: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. Advances in knowledge: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma. PMID:23934965

WE-H-BRA-01: BEST IN PHYSICS (THERAPY): Nano-Dosimetric Kinetic Model for Variable Relative Biological Effectiveness of Proton and Ion Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abolfath, R; Bronk, L; Titt, U.

2016-06-15

Purpose: Recent clonogenic cell survival and γH2AX studies suggest proton relative biological effectiveness (RBE) may be a non-linear function of linear energy transfer (LET) in the distal edge of the Bragg peak and beyond. We sought to develop a multiscale model to account for non-linear response phenomena to aid in the optimization of intensity-modulated proton therapy. Methods: The model is based on first-principle simulations of proton track structures, including secondary ions, and an analytical derivation of the dependence on particle LET of the linear-quadratic (LQ) model parameters α and β. The derived formulas are an extension of the microdosimetric kineticmore » (MK) model that captures dissipative track structures and non-Poissonian distribution of DNA damage at the distal edge of the Bragg peak and beyond. Monte Carlo simulations were performed to confirm the non-linear dose-response characteristics arising from the non-Poisson distribution of initial DNA damage. Results: In contrast to low LET segments of the proton depth dose, from the beam entrance to the Bragg peak, strong deviations from non-dissipative track structures and Poisson distribution in the ionization events in the Bragg peak distal edge govern the non-linear cell response and result in the transformation α=(1+c-1 L) α-x+2(c-0 L+c-2 L^2 )(1+c-1 L) β-x and β=(1+c-1 L)^2 β-x. Here L is the charged particle LET, and c-0,c-1, and c-2 are functions of microscopic parameters and can be served as fitting parameters to the cell-survival data. In the low LET limit c-1, and c-2 are negligible hence the linear model proposed and used by Wilkins-Oelfke for the proton treatment planning system can be retrieved. The present model fits well the recent clonogenic survival data measured recently in our group in MDACC. Conclusion: The present hybrid method provides higher accuracy in calculating the RBE-weighted dose in the target and normal tissues.« less

The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range

PubMed Central

Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTOrganic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose-dependent. WHAT THIS STUDY ADDSRepaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range. AIMS To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. METHODS Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of ≥1 week. RESULTS The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype. CONCLUSIONS The effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range. PMID:18823304

Characterization of the ultrasonic attenuation coefficient and its frequency dependence in a polymer gel dosimeter.

PubMed

Crescenti, Remo A; Bamber, Jeffrey C; Partridge, Mike; Bush, Nigel L; Webb, Steve

2007-11-21

Research on polymer-gel dosimetry has been driven by the need for three-dimensional dosimetry, and because alternative dosimeters are unsatisfactory or too slow for that task. Magnetic resonance tomography is currently the most well-developed technique for determining radiation-induced changes in polymer structure, but quick low-cost alternatives remain of significant interest. In previous work, ultrasound attenuation and speed of sound were found to change as a function of absorbed radiation dose in polymer-gel dosimeters, although the investigations were restricted to one ultrasound frequency. Here, the ultrasound attenuation coefficient mu in one polymer gel (MAGIC) was investigated as a function of radiation dose D and as a function of ultrasonic frequency f in a frequency range relevant for imaging dose distributions. The nonlinearity of the frequency dependence was characterized, fitting a power-law model mu = af(b); the fitting parameters were examined for potential use as additional dose readout parameters. In the observed relationship between the attenuation coefficient and dose, the slopes in a quasi-linear dose range from 0 to 30 Gy were found to vary with the gel batch but lie between 0.0222 and 0.0348 dB cm(-1) Gy(-1) at 2.3 MHz, between 0.0447 and 0.0608 dB cm(-1) Gy(-1) at 4.1 MHz and between 0.0663 and 0.0880 dB cm(-1) Gy(-1) at 6.0 MHz. The mean standard deviation of the slope for all samples and frequencies was 15.8%. The slope was greater at higher frequencies, but so were the intra-batch fluctuations and intra-sample standard deviations. Further investigations are required to overcome the observed variability, which was largely associated with the sample preparation technique, before it can be determined whether any frequency is superior to others in terms of accuracy and precision in dose determination. Nevertheless, lower frequencies will allow measurements through larger samples. The fit parameter a of the frequency dependence, describing the attenuation coefficient at 1 MHz, was found to be dose dependent, which is consistent with our expectations, as polymerization is known to be associated with increased absorption of ultrasound. No significant dose dependence was found for the fit parameter b, which describes the nonlinearity with frequency. This is consistent with the increased absorption being due to the introduction of new relaxation processes with characteristic frequencies similar to those of existing processes. The data presented here will help with optimizing the design of future 3D dose-imaging systems using ultrasound methods.

Real-time volumetric relative dosimetry for magnetic resonance—image-guided radiation therapy (MR-IGRT)

NASA Astrophysics Data System (ADS)

Lee, Hannah J.; Kadbi, Mo; Bosco, Gary; Ibbott, Geoffrey S.

2018-02-01

The integration of magnetic resonance imaging (MRI) with linear accelerators (linac) has enabled the use of 3D MR-visible gel dosimeters for real-time verification of volumetric dose distributions. Several iron-based radiochromic 3D gels were created in-house then imaged and irradiated in a pre-clinical 1.5 T-7 MV MR-Linac. MR images were acquired using a range of balanced-fast field echo (b-FFE) sequences during irradiation to assess the contrast and dose response in irradiated regions and to minimize the presence of MR artifacts. Out of four radiochromic 3D gel formulations, the FOX 3D gel was found to provide superior MR contrast in the irradiated regions. The FOX gels responded linearly with respect to real-time dose and the signal remained stable post-irradiation for at least 20 min. The response of the FOX gel also was found to be unaffected by the radiofrequency and gradient fields created by the b-FFE sequence during irradiation. A reusable version of the FOX gel was used for b-FFE sequence optimization to reduce artifacts by increasing the number of averages at the expense of temporal resolution. Regardless of the real-time MR sequence used, the FOX 3D gels responded linearly to dose with minimal magnetic field effects due to the strong 1.5 T field or gradient fields present during imaging. These gels can easily be made in-house using non-reusable and reusable formulations depending on the needs of the clinic, and the results of this study encourage further applications of 3D gels for MR-IGRT applications.

Monte Carlo study of neutron-ambient dose equivalent to patient in treatment room.

PubMed

Mohammadi, A; Afarideh, H; Abbasi Davani, F; Ghergherehchi, M; Arbabi, A

2016-12-01

This paper presents an analytical method for the calculation of the neutron ambient dose equivalent H* (10) regarding patients, whereby the different concrete types that are used in the surrounding walls of the treatment room are considered. This work has been performed according to a detailed simulation of the Varian 2300C/D linear accelerator head that is operated at 18MV, and silver activation counter as a neutron detector, for which the Monte Carlo MCNPX 2.6 code is used, with and without the treatment room walls. The results show that, when compared to the neutrons that leak from the LINAC, both the scattered and thermal neutrons are the major factors that comprise the out-of field neutron dose. The scattering factors for the limonite-steel, magnetite-steel, and ordinary concretes have been calculated as 0.91±0.09, 1.08±0.10, and 0.371±0.01, respectively, while the corresponding thermal factors are 34.22±3.84, 23.44±1.62, and 52.28±1.99, respectively (both the scattering and thermal factors are for the isocenter region); moreover, the treatment room is composed of magnetite-steel and limonite-steel concretes, so the neutron doses to the patient are 1.79 times and 1.62 times greater than that from an ordinary concrete composition. The results also confirm that the scattering and thermal factors do not depend on the details of the chosen linear accelerator head model. It is anticipated that the results of the present work will be of great interest to the manufacturers of medical linear accelerators. Copyright © 2016. Published by Elsevier Ltd.

Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects

NASA Technical Reports Server (NTRS)

Vaksman, Z.; Boyd, J. L.; Wang, Z.; Putcha, L.

2005-01-01

The objective of this study is to compare cognitive function tests, Automated Neurological Assessment Metrics (ANAM) based Readiness Evaluation System (ARES(Registered TradeMark)) on a Palm Pilot and Windows based Spaceflight Cognitive Assessment Tool (WinSCAT(Registered TradeMark)) on a personal computer (PC) to assess performance effects of promethazine (PMZ) after administration to human subjects. In a randomized placebo-controlled cross-over design, subjects received 12.5, 25, and 50 mg intramuscular (IM) PMZ or a placebo and completed 14 sessions with WinSCAT(Registered TradeMark) (v. 1.26) and ARES(Registered TradeMark) (v. 1.27) consecutively for 72 h post dose. Maximum plasma concentrations (4.25, 6.25 and 13.33 ng/ml) were linear with dose and were achieved by 0.75, 8, and 24 h after dosing for the three doses, respectively. No significant differences in cognitive function after PMZ dosing were detected using WinSCAT(Registered TradeMark), however, tests from ARES(Registered TradeMark) demonstrated concentration dependent decrements in reaction time associated with PMZ dose.

Sol-gel derived copper-doped silica glass as a sensitive material for X-ray beam dosimetry

NASA Astrophysics Data System (ADS)

Capoen, Bruno; Hamzaoui, Hicham El; Bouazaoui, Mohamed; Ouerdane, Youcef; Boukenter, Aziz; Girard, Sylvain; Marcandella, Claude; Duhamel, Olivier

2016-01-01

The light emission from a sol-gel-derived Cu-doped silica glass was studied under 10 keV X-ray irradiation using a fibered setup. Both radioluminescence (RL) and optically stimulated luminescence (OSL) were analyzed at different high dose rates up to 50 Gy/s and for different exposure times, yielding accumulated doses up to 50 kGy (in SiO2). Even if a darkening effect appears at this dose level, the material remains X-sensitive after exposure to several kGy. At low dose rate, the scintillation mechanisms are similar to photoluminescence, involving the Cu+ ions electronic levels, contrary to the nonlinear domain (for dose rates higher than 30 Gy/s). This RL, as well as the OSL, could be exploited in their linear domain to measure doses as high as 3 kGy. A thorough study of the OSL signal has shown that it must be employed with caution in order to take the fading phenomenon and the response dependency on stimulation source intensity into consideration.

The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative Biological Effectiveness.

PubMed

Jones, B; McMahon, S J; Prise, K M

2018-05-01

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2-1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed. Copyright © 2018. Published by Elsevier Ltd.

Glucuronidation and Sulfation Kinetics of Diflunisal in Man.

NASA Astrophysics Data System (ADS)

Loewen, Gordon Rapheal

Diflunisal is a nonsteroidal anti-inflammatory drug used in the treatment of arthritis and musculoskeletal pain. Diflunisal exhibits concentration- and dose-dependent kinetics, the mechanism of which has not been determined. The purpose of this study was to determine the mechanism(s) responsible for non-linear disposition of diflunisal and to examine environmental factors which may affect the elimination of diflunisal. The metabolites of diflunisal, including a new metabolite, the sulphate conjugate, were purified by column and semi-preparative high pressure liquid chromatography. Assays for the quantitation of diflunisal and conjugates in urine and diflunisal in plasma were developed. Plasma protein binding of diflunisal in blank plasma and in plasma obtained following multiple doses of diflunisal was determined by equilibrium dialysis. Total body clearance of diflunisal decreased when dose increased from 100 to 750 mg. Total clearance increased when dose increased from 750 to 1000 mg. The percent of recovered dose eliminated as the acyl glucuronide decreased and the percent eliminated as the sulphate increased with increasing dose of diflunisal. Plasma protein binding of diflunisal was concentration dependent over a range of diflunisal plasma concentrations of 3 to 257 mug/ml. Total clearance, and to a lesser degree, unbound clearance of diflunisal were decreased following multiple dose administration of 250 and 500 mg diflunisal. Percent of recovered dose eliminated as the acyl glucuronide decreased and percent eliminated as the sulphate conjugate increased following multiple dosing. Plasma protein binding of diflunisal was similar in blank plasma and plasma obtained at steady state. Unbound clearance of diflunisal exceeded liver plasma flow. Frequency distributions of the elimination of the conjugates of diflunisal were normally distributed. Sex, smoking, and use of vitamins or oral contraceptives were identified as factors which may affect the elimination of diflunisal.

Methadone and Metabolites in Hair of Methadone-Assisted Pregnant Women and Their Infants

PubMed Central

Himes, Sarah K; Goodwin, Robert S; Rock, Colleen M; Jones, Hendrée E; Johnson, Rolley E; Wilkins, Diana G; Huestis, Marilyn A

2012-01-01

Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes. Materials and Methods Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3cm), washed (maternal hair only) and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) by liquid chromatography tandem mass spectrometry. Results There was large inter-subject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, EMDP or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone’s induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference or amount of neonatal morphine pharmacotherapy. Maternal cumulative 3rd trimester methadone dose was positively correlated with infant birth weight. Conclusion Methadone and EDDP in pregnant women’s hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure. PMID:22495425

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.

PubMed

Larsen, Malte Selch; Keizer, Ron; Munro, Gordon; Mørk, Arne; Holm, René; Savic, Rada; Kreilgaard, Mads

2016-05-01

Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia. A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous). The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m  = 44.1 mg/kg, V max  = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma  = 16.7 μg/mL, EC 50, brain  = 3.3 μg/mL). The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

Assessment of Ethylene Vinyl-Acetato Copolymer (EVA) Samples Bombarded by Gamma Radiation via Linearity Analyses

NASA Astrophysics Data System (ADS)

de Oliveira, L. N.; do Nascimento, E. O.; Schimidt, F.; Antonio, P. L.; Caldas, L. V. E.

2018-03-01

Materials with the potential to become dosimeters are of interest in radiation physics. In this research, the materials were analyzed and compared in relation to their linearity ranges. Samples of ethylene vinyl-acetate copolymer (EVA) were irradiated with doses from 10 Gy to 10 kGy using a 60Co Gamma-Cell system 220 and evaluated with the FTIR technique. The linearity analyses were applied through two methodologies, searching for linear regions in their response. The results show that both applied analyses indicate linear regions in defined dose interval. The radiation detectors EVA can be useful for radiation dosimetry in intermediate and high doses.

Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

PubMed Central

Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

2014-01-01

Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

Film Dosimetry for Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Benites-Rengifo, J.; Martínez-Dávalos, A.; Celis, M.; Lárraga, J.

2004-09-01

Intensity Modulated Radiation Therapy (IMRT) is an oncology treatment technique that employs non-uniform beam intensities to deliver highly conformal radiation to the targets while minimizing doses to normal tissues and critical organs. A key element for a successful clinical implementation of IMRT is establishing a dosimetric verification process that can ensure that delivered doses are consistent with calculated ones for each patient. To this end we are developing a fast quality control procedure, based on film dosimetry techniques, to be applied to the 6 MV Novalis linear accelerator for IMRT of the Instituto Nacional de Neurología y Neurocirugía (INNN) in Mexico City. The procedure includes measurements of individual fluence maps for a limited number of fields and dose distributions in 3D using extended dose-range radiographic film. However, the film response to radiation might depend on depth, energy and field size, and therefore compromise the accuracy of measurements. In this work we present a study of the dependence of Kodak EDR2 film's response on the depth, field size and energy, compared with those of Kodak XV2 film. The first aim is to devise a fast and accurate method to determine the calibration curve of film (optical density vs. doses) commonly called a sensitometric curve. This was accomplished by using three types of irradiation techniques: Step-and-shoot, dynamic and static fields.

Polymer-gel formation and reformation on irradiation of tertiary-butyl acrylate

NASA Astrophysics Data System (ADS)

Yao, Tiantian; Denkova, Antonia G.; Warman, John M.

2014-04-01

The purpose of the present research was to provide a radiation-chemical basis for the use of tertiary-butyl acrylate gels in radio-fluorogenic dose-imaging applications (Warman et al. 2011a,b, 2013a,b). The radiation-induced polymerization of tertiary-butyl acrylate (TBA) results in the formation of a transparent gel with an optical density lower than 0.1 cm-1 from 600 nm down to 315 nm. The fractional monomer-to-polymer conversion, CM, determined gravimetrically, increases super-linearly with dose, D Gy. Up to CM≈40%, and over the dose rate range D‧=3.5 to 49 cGy s-1, the dose dependence is given by CM=[1+ACM]KD/√D‧ with K=1.43×10-3 Gy-0.5 s-0.5 and A=0.70. For D‧=3.5 cGy s-1 the average polymer size is estimated to be 1.2×105 monomer units or 17 megadalton. For CM≥10% the gel is quasi-rigid, displaying little tendency to flow on a timescale of an hour or more. After removal of monomer by evacuation, the gel can be reformed by adding a volume of monomer to the remaining polymer equal to that removed and allowing this to swell for several days. The dose and dose rate dependence of radiation-induced monomer conversion in the reformed gel show no evidence of a discontinuity caused by the intervening evacuation and reformation procedures.

Dosimetric Evaluation Between Megavoltage Cone-Beam Computed Tomography and Body Mass Index for Intracranial, Thoracic, and Pelvic Localization

DOE Office of Scientific and Technical Information (OSTI.GOV)

VanAntwerp, April E.; Raymond, Sarah M., E-mail: raymons9@ccf.org; Addington, Mark C.

2011-10-01

The aim of this study was to evaluate radiation dose for organs at risk (OAR) within the cranium, thorax, and pelvis from megavoltage cone-beam computed tomography (MV-CBCT). Using a clinical treatment planning system, CBCT doses were calculated from 60 patient datasets using 27.4 x 27.4 cm{sup 2} field size and 200{sup o} arc length. The body mass indices (BMIs) for these patients range from 17.2-48.4 kg/m{sup 2}. A total of 60 CBCT plans were created and calculated with heterogeneity corrections, with monitor units (MU) that varied from 8, 4, and 2 MU per plan. The isocenters of these plans weremore » placed at defined anatomical structures. The maximum dose, dose to the isocenter, and mean dose to the selected critical organs were analyzed. The study found that maximum and isocenter doses were weakly associated with BMI, but linearly associated with the total MU. Average maximum/isocenter doses in the cranium were 10.0 ({+-} 0.18)/7.0 ({+-} 0.08) cGy, 5.0 ({+-} 0.09)/3.5 ({+-} 0.05) cGy, and 2.5 ({+-} .04)/1.8 ({+-} 0.05) cGy for 8, 4, and 2 MU, respectively. Similar trends but slightly larger maximum/isocenter doses were found in the thoracic and pelvic regions. For the cranial region, the average mean doses with a total of 8 MU to the eye, lens, and brain were 9.7 ({+-} 0.12) cGy, 9.1 ({+-} 0.16) cGy, and 7.2 ({+-} 0.10) cGy, respectively. For the thoracic region, the average mean doses to the lung, heart, and spinal cord were 6.6 ({+-} 0.05) cGy, 6.9 ({+-} 1.2) cGy, and 4.7 ({+-} 0.8) cGy, respectively. For the pelvic region, the average mean dose to the femoral heads was 6.4 ({+-} 1.1) cGy. The MV-CBCT doses were linearly associated with the total MU but weakly dependent on patients' BMIs. Daily MV-CBCT has a cumulative effect on the total body dose and critical organs, which should be carefully considered for clinical impacts.« less

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Zaghian, M; Lim, G

2015-06-15

Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less

Using state variables to model the response of tumour cells to radiation and heat: a novel multi-hit-repair approach.

PubMed

Scheidegger, Stephan; Fuchs, Hans U; Zaugg, Kathrin; Bodis, Stephan; Füchslin, Rudolf M

2013-01-01

In order to overcome the limitations of the linear-quadratic model and include synergistic effects of heat and radiation, a novel radiobiological model is proposed. The model is based on a chain of cell populations which are characterized by the number of radiation induced damages (hits). Cells can shift downward along the chain by collecting hits and upward by a repair process. The repair process is governed by a repair probability which depends upon state variables used for a simplistic description of the impact of heat and radiation upon repair proteins. Based on the parameters used, populations up to 4-5 hits are relevant for the calculation of the survival. The model describes intuitively the mathematical behaviour of apoptotic and nonapoptotic cell death. Linear-quadratic-linear behaviour of the logarithmic cell survival, fractionation, and (with one exception) the dose rate dependencies are described correctly. The model covers the time gap dependence of the synergistic cell killing due to combined application of heat and radiation, but further validation of the proposed approach based on experimental data is needed. However, the model offers a work bench for testing different biological concepts of damage induction, repair, and statistical approaches for calculating the variables of state.

Evaluation of the dosimetric properties of a diode detector for small field proton radiosurgery.

PubMed

McAuley, Grant A; Teran, Anthony V; Slater, Jerry D; Slater, James M; Wroe, Andrew J

2015-11-08

The small fields and sharp gradients typically encountered in proton radiosurgery require high spatial resolution dosimetric measurements, especially below 1-2 cm diameters. Radiochromic film provides high resolution, but requires postprocessing and special handling. Promising alternatives are diode detectors with small sensitive volumes (SV) that are capable of high resolution and real-time dose acquisition. In this study we evaluated the PTW PR60020 proton dosimetry diode using radiation fields and beam energies relevant to radiosurgery applications. Energies of 127 and 157 MeV (9.7 to 15 cm range) and initial diameters of 8, 10, 12, and 20mm were delivered using single-stage scattering and four modulations (0, 15, 30, and 60mm) to a water tank in our treatment room. Depth dose and beam profile data were compared with PTW Markus N23343 ionization chamber, EBT2 Gafchromic film, and Monte Carlo simulations. Transverse dose profiles were measured using the diode in "edge-on" orientation or EBT2 film. Diode response was linear with respect to dose, uniform with dose rate, and showed an orientation-dependent (i.e., beam parallel to, or perpendicular to, detector axis) response of less than 1%. Diodevs. Markus depth-dose profiles, as well as Markus relative dose ratio vs. simulated dose-weighted average lineal energy plots, suggest that any LET-dependent diode response is negligible from particle entrance up to the very distal portion of the SOBP for the energies tested. Finally, while not possible with the ionization chamber due to partial volume effects, accurate diode depth-dose measurements of 8, 10, and 12 mm diameter beams were obtained compared to Monte Carlo simulations. Because of the small SV that allows measurements without partial volume effects and the capability of submillimeter resolution (in edge-on orientation) that is crucial for small fields and high-dose gradients (e.g., penumbra, distal edge), as well as negligible LET dependence over nearly the full the SOBP, the PTW proton diode proved to be a useful high-resolution, real-time metrology device for small proton field radiation measurements such as would be encountered in radiosurgery applications.

Cosmetic wastewater treatment by the ZVI/H2O2 process.

PubMed

Bogacki, Jan; Marcinowski, Piotr; Zapałowska, Ewa; Maksymiec, Justyna; Naumczyk, Jeremi

2017-10-01

The ZVI/H 2 O 2 process was applied for cosmetic wastewater treatment. Two commercial zero-valent iron (ZVI) types with different granulations were chosen: Hepure Ferrox PRB and Hepure Ferrox Target. In addition, the pH and stirring method influence on ZVI/H 2 O 2 process efficiency was studied. During the ZVI and ZVI/H 2 O 2 processes, linear Fe ions concentration increase was observed. The addition of H 2 O 2 significantly accelerated the iron dissolution process. The highest COD removal was obtained using finer ZVI (Hepure Ferrox Target) for doses of reagents ZVI/H 2 O 2 1500/1600 mg/L, in a H 2 O 2 /COD weight ratio 2:1, at pH 3.0 with stirring on a magnetic stirrer. After 120 min of the process, 84.0% COD removal (from 796 to 127 mg/L) was achieved. It was found that the efficiency of the process depends, as in the case of the Fenton process, on the ratio of the reagents (ZVI/H 2 O 2 ) and their dose in relation to the COD (H 2 O 2 /COD) but does not depend on the dose of the iron itself. Statistical analysis confirms that COD removal efficiency depends primarily on H 2 O 2 /COD ratio and ZVI granulation, but ZVI dose influence is not statistically significant. The head space, solid-phase microextraction, gas chromatography, mass spectrometry results confirm high efficiency of the ZVI/H 2 O 2 process.

Experimental design and statistical analysis for three-drug combination studies.

PubMed

Fang, Hong-Bin; Chen, Xuerong; Pei, Xin-Yan; Grant, Steven; Tan, Ming

2017-06-01

Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures from additivity depends on dose-response shapes of individual constituent drugs. Thus, different classes of drugs of different dose-response shapes need to be treated as a separate case. Our application and case studies develop dose finding and sample size method for detecting departures from additivity with several common (linear and log-linear) classes of single dose-response curves. Furthermore, utilizing the geometric features of the interaction index, we propose a nonparametric model to estimate the interaction index surface by B-spine approximation and derive its asymptotic properties. Utilizing the method, we designed and analyzed a combination study of three anticancer drugs, PD184, HA14-1, and CEP3891 inhibiting myeloma H929 cell line. To our best knowledge, this is the first ever three drug combinations study performed based on the original 4D dose-response surface formed by dose ranges of three drugs.

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Land, C.E.; Boice, J.D. Jr.; Shore, R.E.

1980-08-01

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years atmore » exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.« less

SU-F-T-263: Dosimetric Characteristics of the Cine Acquisition Mode of An A-Si EPID

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bawazeer, O; Deb, P; Sarasanandarajah, S

2016-06-15

Purpose: To investigate the dosimetric characteristics of Varian a-Si-500 electronic portal imaging device (EPID) operated in cine mode particularly considering linearity with delivered dose, dose rate, field size, phantom thickness, MLC speed and common IMRT fields. Methods: The EPID that attached to a Varian Clinac 21iX linear accelerator, was irradiated with 6 and 18 MV using 600 MU/min. Image acquisition is controlled by the IAS3 software, Trigger delay was 6 ms, BeamOnDelay and FrameStartDelay were zero. Different frame rates were utilized. Cine mode response was calculated using MATLAB as summation of mean pixel values in a region of interest ofmore » the acquired images. The performance of cine mode was compared to integrated mode and dose measurements in water using CC13 ionization chamber. Results: Figure1 illustrates that cine mode has nonlinear response for small MU, when delivering 10 MU was about 0.5 and 0.64 for 6 and 18 MV respectively. This is because the missing acquired images that were calculated around four images missing in each delivery. With the increase MU the response became linear and comparable with integrated mode and ionization chamber within 2%. Figure 2 shows that cine mode has comparable response with integrated mode and ionization chamber within 2% with changing dose rate for 10 MU delivered. This indicates that the dose rate change has no effect on nonlinearity of cine mode response. Except nonlinearity, cine mode is well matched to integrated mode response within 2% for field size, phantom thickness, MLC speed dependences. Conclusion: Cine mode has similar dosimetric characteristics to integrated mode with open and IMRT fields, and the main limitation with cine mode is missing images. Therefore, the calibration of EPID images with this mode should be run with large MU, and when IMRT verification field has low MU, the correction for missing images are required.« less

Synthetic detergents induced-biochemical and histological changes in skin of guinea pigs.

PubMed

Agarwal, C; Mathur, A K; Gupta, B N; Singh, A; Shanker, R

1990-06-01

The linear alkylbenzene sulphonate (LAS) based synthetic detergents-induced decrease in lipid peroxydation and increase in histamine content in exposed skin of guinea pigs in a dose-dependent manner. Histopathological alterations of exposed skin included moderate degree of hyperkeratinization at lower concentration but necrosis, scarring, sloughing as well as discontinuity of epidermis at higher concentrations. The results shows that the contact of skin with detergents causes dermal toxicity.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings.

PubMed

Chen, Jia-Yan; Zhu, Hong-Cheng; Guo, Qing; Shu, Zheng; Bao, Xu-Hui; Sun, Feng; Qin, Qin; Yang, Xi; Zhang, Chi; Cheng, Hong-Yan; Sun, Xin-Chen

2016-01-01

To investigate any potential association between wine and breast cancer risk. We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Linear-quadratic dose kinetics or dose-dependent repair/misrepair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braby, L.A.; Nelson, J.M.

1991-09-01

Models for the response of cells exposed to low LET radiation can be grouped into three general types on the basis of assumptions about the nature of the interaction which results in the shoulder of the survival curve. The three forms of interaction are (1) sublethal damage becoming lethal, (2) potentially lethal damage becoming irreparable, and (3) potentially lethal damage saturating'' a repair system. The effects that these three forms of interaction would have on the results of specific types of experiments are investigated. Comparisons with experimental results indicate that only the second type is significant in determining the responsemore » of typical cultured mammalian cells. 5 refs., 2 figs.« less

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

PubMed Central

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

2015-01-01

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. PMID:26445334

SU-E-T-607: Performance Quantification of the Nine Detectors Used for Dosimetry Measurements in Advanced Radiation Therapy Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markovic, M; Stathakis, S; Jurkovic, I

2015-06-15

Purpose: The purpose of this study was to quantify performance of the nine detectors used for dosimetry measurements in advanced radiation therapy treatments. Methods: The 6 MV beam was utilized for measurements of the field sizes with the lack of lateral charge particle equilibrium. For dose fidelity aspect, energy dependence was studied by measuring PDD and profiles at different depths. The volume effect and its influence on the measured dose profiles have been observed by measuring detector’s response function. Output factor measurements with respect to change in energy spectrum have been performed and collected data has been analyzed. The linearitymore » of the measurements with the dose delivered has been evaluated and relevant comparisons were done. Results: The measured values of the output factors with respect to change in energy spectrum indicated presence of the energy dependence. The detectors with active volume size ≤ 0.3 mm3 maximum deviation from the mean is 5.6% for the field size 0.5 x 0.5 cm2 while detectors with active volume size > 0.3 mm3 have maximum deviation from the mean 7.1%. Linearity with dose at highest dose rate examined for diode detectors showed maximum deviation of 4% while ion chambers showed maximum deviation of 2.2%. Dose profiles showed energy dependence at shallow depths (surface to dmax) influenced by low energy particles with 12 % maximum deviation from the mean for 5 mm2 field size. In relation to Monte Carlo calculation, the detector’s response function σ values were between (0.42±0.25) mm and (1.2±0.25) mm. Conclusion: All the detectors are appropriate for the dosimetry measurements in advanced radiation therapy treatments. The choice of the detectors has to be determined by the application and the scope of the measurements in respect to energy dependence and ability to accurately resolve dose profiles as well as to it’s intrinsic characteristics.« less

Physical and radiological properties of radiochromic gel as of its composition

NASA Astrophysics Data System (ADS)

Lee, Sang Hoon; Kim, Juree; Shim, Su Jung; Chang, Kyung Hwan; Lim, Sangwook; Huh, Hyun Do; Shin, Dong Oh; Cho, Sam Ju

2014-04-01

In the research, we evaluated the use of leuco crystal violet (LCV) gel as a dosimeter for therapeutic radiation by investigating its optical characteristics at various component concentrations. We also investigated the aging effect of the LCV gel at different beam energies, doserates, and dosing times to evaluate the LCV's applicability to radiation therapy. We confirmed that the optimal optical wavelength of the LCV gel dosimeter was 600 nm. The dose sensitivity increased with increasing concentration of LCV; however, the optimal concentration was 1 mM LCV because the transparency of the gel dosimeter is important for use in optical CT scanners. However, the dose sensitivity decreased with increasing concentration of trichloroacetic acid (TAA). Moreover, the transparency of LCV rapidly decreased because of the generation of a white precipitate at TAA concentrations below 25 mM. Thus, an optimal TAA concentration of 30 mM was used in this study. Triton X-100 (8 mM) was identified as the optimal reagent for determining the optimum gel transparency and dose sensitivity. Thus, we present an LCV gel dosimeter composed of 4% gelatin by mass, 1 mM LCV, 30 mM TAA, and 8-mM Triton X-100 for use with an optical CT scanner. We showed good dose linearity up to 30 Gy. There was a little doserate dependency at a beam energy of 6 MV while the doserate dependence was more than 4.2% at a beam energy of 10 MV. To evaluate the energy dependence of the LCV gel dosimeter, we irradiated it at 20 Gy by using 6 MV and 10 MV beams. At the high doserate, the difference in the dose energy dependence was relatively small at approximately 1%, but the difference increased to 4.6% at the low doserate. With respect to the radiation absorbance at a photon energy of 6 MV, the absorbance at an electron energy of 6 MeV decreased by 5.4%, and the absorbances at 9, 12, and 15 MeV increased by 3, 18.7, and 12.2%, respectively. Furthermore, the aging effect was larger in the low-dose group then in the high-dose group. Moreover, we observed that the absorbance between 24 and 48 h after irradiation increased by approximately 5% at 5 Gy. For gel groups tested at high doses, the aging effect was reduced by approximately 1%.

Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus.

PubMed

Vajda, Eric G; Logan, Douglas; Lasseter, Kenneth; Armas, Danielle; Plotkin, Diane J; Pipkin, J D; Li, Yong-Xi; Zhou, Rong; Klein, David; Wei, Xiaoxiong; Dilzer, Stacy; Zhi, Lin; Marschke, Keith B

2017-01-01

To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD-6972, in healthy subjects and subjects with type 2 diabetes (T2DM). In the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days. LGD-6972 had linear plasma pharmacokinetics consistent with once-daily dosing that was comparable in healthy and T2DM subjects. Dose-dependent decreases in fasting plasma glucose were observed in all groups with a maximum of 3.15 mmol/L (56.8 mg/dL) on day 14 in T2DM subjects. LGD-6972 also reduced plasma glucose in the postprandial state. Dose-dependent increases in fasting plasma glucagon were observed, but glucagon levels decreased and insulin levels increased after an oral glucose load in T2DM subjects. LGD-6972 was well tolerated at the doses tested without dose-related or clinically meaningful changes in clinical laboratory parameters. No subject experienced hypoglycaemia. Inhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Gafchromic EBT‐XD film: Dosimetry characterization in high‐dose, volumetric‐modulated arc therapy

PubMed Central

Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-01-01

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT‐XD films have been designed for optimal performance in the 40–4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose‐response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high‐dose volumetric‐modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0–4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter‐free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose‐rate dependence. For clinical examinations, we compared the dose distribution measured with EBT‐XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT‐XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ∼3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ∼1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ∼1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film‐ measured and treatment planning system (TPS)‐calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. PACS number(s): 87.56 Fc PMID:27929504

Estimating organ doses from tube current modulated CT examinations using a generalized linear model.

PubMed

Bostani, Maryam; McMillan, Kyle; Lu, Peiyun; Kim, Grace Hyun J; Cody, Dianna; Arbique, Gary; Greenberg, S Bruce; DeMarco, John J; Cagnon, Chris H; McNitt-Gray, Michael F

2017-04-01

Currently, available Computed Tomography dose metrics are mostly based on fixed tube current Monte Carlo (MC) simulations and/or physical measurements such as the size specific dose estimate (SSDE). In addition to not being able to account for Tube Current Modulation (TCM), these dose metrics do not represent actual patient dose. The purpose of this study was to generate and evaluate a dose estimation model based on the Generalized Linear Model (GLM), which extends the ability to estimate organ dose from tube current modulated examinations by incorporating regional descriptors of patient size, scanner output, and other scan-specific variables as needed. The collection of a total of 332 patient CT scans at four different institutions was approved by each institution's IRB and used to generate and test organ dose estimation models. The patient population consisted of pediatric and adult patients and included thoracic and abdomen/pelvis scans. The scans were performed on three different CT scanner systems. Manual segmentation of organs, depending on the examined anatomy, was performed on each patient's image series. In addition to the collected images, detailed TCM data were collected for all patients scanned on Siemens CT scanners, while for all GE and Toshiba patients, data representing z-axis-only TCM, extracted from the DICOM header of the images, were used for TCM simulations. A validated MC dosimetry package was used to perform detailed simulation of CT examinations on all 332 patient models to estimate dose to each segmented organ (lungs, breasts, liver, spleen, and kidneys), denoted as reference organ dose values. Approximately 60% of the data were used to train a dose estimation model, while the remaining 40% was used to evaluate performance. Two different methodologies were explored using GLM to generate a dose estimation model: (a) using the conventional exponential relationship between normalized organ dose and size with regional water equivalent diameter (WED) and regional CTDI vol as variables and (b) using the same exponential relationship with the addition of categorical variables such as scanner model and organ to provide a more complete estimate of factors that may affect organ dose. Finally, estimates from generated models were compared to those obtained from SSDE and ImPACT. The Generalized Linear Model yielded organ dose estimates that were significantly closer to the MC reference organ dose values than were organ doses estimated via SSDE or ImPACT. Moreover, the GLM estimates were better than those of SSDE or ImPACT irrespective of whether or not categorical variables were used in the model. While the improvement associated with a categorical variable was substantial in estimating breast dose, the improvement was minor for other organs. The GLM approach extends the current CT dose estimation methods by allowing the use of additional variables to more accurately estimate organ dose from TCM scans. Thus, this approach may be able to overcome the limitations of current CT dose metrics to provide more accurate estimates of patient dose, in particular, dose to organs with considerable variability across the population. © 2017 American Association of Physicists in Medicine.

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp; Törnqvist, Margareta; Nishiyama, Naohiro

2014-03-15

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at differentmore » time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels. • diHOPrVal is considered a useful exposure and in vivo dose marker of G.« less

The question of nonlinearity in the dose-response relation between particulate matter air pollution and mortality: can Akaike's Information Criterion be trusted to take the right turn?

PubMed

Roberts, Steven; Martin, Michael A

2006-12-15

The shape of the dose-response relation between particulate matter air pollution and mortality is crucial for public health assessment, and departures of this relation from linearity could have important regulatory consequences. A number of investigators have studied the shape of the particulate matter-mortality dose-response relation and concluded that the relation could be adequately described by a linear model. Some of these researchers examined the hypothesis of linearity by comparing Akaike's Information Criterion (AIC) values obtained under linear, piecewise linear, and spline alternative models. However, at the current time, the efficacy of the AIC in this context has not been assessed. The authors investigated AIC as a means of comparing competing dose-response models, using data from Cook County, Illinois, for the period 1987-2000. They found that if nonlinearities exist, the AIC is not always successful in detecting them. In a number of the scenarios considered, AIC was equivocal, picking the correct simulated dose-response model about half of the time. These findings suggest that further research into the shape of the dose-response relation using alternative model selection criteria may be warranted.

Optimization of Monte Carlo dose calculations: The interface problem

NASA Astrophysics Data System (ADS)

Soudentas, Edward

1998-05-01

High energy photon beams are widely used for radiation treatment of deep-seated tumors. The human body contains many types of interfaces between dissimilar materials that affect dose distribution in radiation therapy. Experimentally, significant radiation dose perturbations has been observed at such interfaces. The EGS4 Monte Carlo code was used to calculate dose perturbations at boundaries between dissimilar materials (such as bone/water) for 60Co and 6 MeV linear accelerator beams using a UNIX workstation. A simple test of the reliability of a random number generator was also developed. A systematic study of the adjustable parameters in EGS4 was performed in order to minimize calculational artifacts at boundaries. Calculations of dose perturbations at boundaries between different materials showed that there is a 12% increase in dose at water/bone interface, and a 44% increase in dose at water/copper interface. with the increase mainly due to electrons produced in water and backscattered from the high atomic number material. The dependence of the dose increase on the atomic number was also investigated. The clinically important case of using two parallel opposed beams for radiation therapy was investigated where increased doses at boundaries has been observed. The Monte Carlo calculations can provide accurate dosimetry data under conditions of electronic non-equilibrium at tissue interfaces.

Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu, E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.

2014-02-15

Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was atmore » the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional radiotherapy. A significant portion of the tumor volume received a very large dose in grid therapy, which ensures significant tumor cell killing in these regions. Conversely, some areas received a relatively small dose, thereby sparing interspersed normal cells and increasing radiation tolerance. The radiobiology modeling results indicated that grid therapy could be useful for treating acutely responding melanomas infiltrating radiosensitive normal tissues. The theoretical model predictions were supported by the clinical outcomes. Conclusions: Grid therapy functions by selectively killing infiltrating tumor cells and concomitantly sparing interspersed normal cells. The TR depends on the radiosensitivity of the cell population, dose, tumor size, and location. Because the volumes of very high dose regions are small, the LQ model can be used safely to predict the clinical outcomes of grid therapy. When treating melanomas with a dose of 15 Gy or higher, single fraction grid therapy is clearly advantageous for sparing interspersed normal cells. The existence of a threshold fraction dose, which was found in the authors’ theoretical simulations, was confirmed by clinical observations.« less

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

PubMed Central

2009-01-01

Background The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit. PMID:20003238

Single toxin dose-response models revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the fourmore » models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.« less

Errors introduced by dose scaling for relative dosimetry

PubMed Central

Watanabe, Yoichi; Hayashi, Naoki

2012-01-01

Some dosimeters require a relationship between detector signal and delivered dose. The relationship (characteristic curve or calibration equation) usually depends on the environment under which the dosimeters are manufactured or stored. To compensate for the difference in radiation response among different batches of dosimeters, the measured dose can be scaled by normalizing the measured dose to a specific dose. Such a procedure, often called “relative dosimetry”, allows us to skip the time‐consuming production of a calibration curve for each irradiation. In this study, the magnitudes of errors due to the dose scaling procedure were evaluated by using the characteristic curves of BANG3 polymer gel dosimeter, radiographic EDR2 films, and GAFCHROMIC EBT2 films. Several sets of calibration data were obtained for each type of dosimeters, and a calibration equation of one set of data was used to estimate doses of the other dosimeters from different batches. The scaled doses were then compared with expected doses, which were obtained by using the true calibration equation specific to each batch. In general, the magnitude of errors increased with increasing deviation of the dose scaling factor from unity. Also, the errors strongly depended on the difference in the shape of the true and reference calibration curves. For example, for the BANG3 polymer gel, of which the characteristic curve can be approximated with a linear equation, the error for a batch requiring a dose scaling factor of 0.87 was larger than the errors for other batches requiring smaller magnitudes of dose scaling, or scaling factors of 0.93 or 1.02. The characteristic curves of EDR2 and EBT2 films required nonlinear equations. With those dosimeters, errors larger than 5% were commonly observed in the dose ranges of below 50% and above 150% of the normalization dose. In conclusion, the dose scaling for relative dosimetry introduces large errors in the measured doses when a large dose scaling is applied, and this procedure should be applied with special care. PACS numbers: 87.56.Da, 06.20.Dk, 06.20.fb PMID:22955658

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Bartsch, Hauke

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI beforemore » and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.« less

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

PubMed

Dropkin, Greg

2016-11-24

Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

Considerations on the calibration of small thermoluminescent dosimeters used for measurement of beta particle absorbed doses in liquid environments.

PubMed

Demidecki, A J; Williams, L E; Wong, J Y; Wessels, B W; Yorke, E D; Strandh, M; Strand, S E

1993-01-01

An investigation has been carried out on the factors which affect the absolute calibration of thermoluminescent dosimeters (TLDs) used in beta particle absorbed dose evaluations. Four effects on light output (LO) were considered: decay of detector sensitivity with time, finite TLD volume, dose linearity, and energy dependence. Most important of these was the decay of LO with time in culture medium, muscle tissue, and gels. This permanent loss of sensitivity was as large as an order of magnitude over a 21-day interval for the nominally 20-microns-thick disc-shaped CaSO4(Dy) TLDs in gel. Associated leaching of the dosimeter crystals out of the Teflon matrix was observed using scanning electron microscopy. Large channels leading from the outside environment into the TLDs were identified using SEM images. A possibility of batch dependence of fading was indicated. The second most important effect was the apparent reduction of light output due to finite size and increased specific gravity of the dosimeter (volume effect). We estimated this term by calculations as 10% in standard "mini" rods for beta particles from 90Y, but nearly a factor of 3 for 131I beta particles in the same geometry. No significant nonlinearity of the log (light output) with log (absorbed dose) over the range 0.05-20.00 Gy was discovered. Energy dependence of the LO was found to be not detectable, within measurement errors, over the range of 0.60-6.0 MeV mean energy electrons. With careful understanding of these effects, calibration via gel phantom would appear to be an acceptable strategy for mini TLDs used in beta absorbed dose evaluations in media.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of nomograms in LDR-HDR prostate brachytherapy.

PubMed

Pujades, Ma Carmen; Camacho, Cristina; Perez-Calatayud, Jose; Richart, José; Gimeno, Jose; Lliso, Françoise; Carmona, Vicente; Ballester, Facundo; Crispín, Vicente; Rodríguez, Silvia; Tormo, Alejandro

2011-09-01

The common use of nomograms in Low Dose Rate (LDR) permanent prostate brachytherapy (BT) allows to estimate the number of seeds required for an implant. Independent dosimetry verification is recommended for each clinical dosimetry in BT. Also, nomograms can be useful for dose calculation quality assurance and they could be adapted to High Dose Rate (HDR). This work sets nomograms for LDR and HDR prostate-BT implants, which are applied to three different institutions that use different implant techniques. Patients treated throughout 2010 till April 2011 were considered for this study. This example was chosen to be the representative of the latest implant techniques and to ensure consistency in the planning. A sufficient number of cases for both BT modalities, prescription dose and different work methodology (depending on the institution) were taken into account. The specific nomograms were built using the correlation between the prostate volume and some characteristic parameters of each BT modality, such as the source Air Kerma Strength, number of implanted seeds in LDR or total radiation time in HDR. For each institution and BT modality, nomograms normalized to the prescribed dose were obtained and fitted to a linear function. The parameters of the adjustment show a good agreement between data and the fitting. It should be noted that for each institution these linear function parameters are different, indicating that each centre should construct its own nomograms. Nomograms for LDR and HDR prostate brachytherapy are simple quality assurance tools, specific for each institution. Nevertheless, their use should be complementary to the necessary independent verification.

The use of nomograms in LDR-HDR prostate brachytherapy

PubMed Central

Camacho, Cristina; Perez-Calatayud, Jose; Richart, José; Gimeno, Jose; Lliso, Françoise; Carmona, Vicente; Ballester, Facundo; Crispín, Vicente; Rodríguez, Silvia; Tormo, Alejandro

2011-01-01

Purpose The common use of nomograms in Low Dose Rate (LDR) permanent prostate brachytherapy (BT) allows to estimate the number of seeds required for an implant. Independent dosimetry verification is recommended for each clinical dosimetry in BT. Also, nomograms can be useful for dose calculation quality assurance and they could be adapted to High Dose Rate (HDR). This work sets nomograms for LDR and HDR prostate-BT implants, which are applied to three different institutions that use different implant techniques. Material and methods Patients treated throughout 2010 till April 2011 were considered for this study. This example was chosen to be the representative of the latest implant techniques and to ensure consistency in the planning. A sufficient number of cases for both BT modalities, prescription dose and different work methodology (depending on the institution) were taken into account. The specific nomograms were built using the correlation between the prostate volume and some characteristic parameters of each BT modality, such as the source Air Kerma Strength, number of implanted seeds in LDR or total radiation time in HDR. Results For each institution and BT modality, nomograms normalized to the prescribed dose were obtained and fitted to a linear function. The parameters of the adjustment show a good agreement between data and the fitting. It should be noted that for each institution these linear function parameters are different, indicating that each centre should construct its own nomograms. Conclusions Nomograms for LDR and HDR prostate brachytherapy are simple quality assurance tools, specific for each institution. Nevertheless, their use should be complementary to the necessary independent verification. PMID:23346120

Cytogenetic effect of low dose gamma-radiation in Hordeum vulgare seedlings: non-linear dose-effect relationship.

PubMed

Geras'kin, Stanislav A; Oudalova, Alla A; Kim, Jin Kyu; Dikarev, Vladimir G; Dikareva, Nina S

2007-03-01

The induction of chromosome aberrations in Hordeum vulgare germinated seeds was studied after ionizing irradiation with doses in the range of 10-1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose was found to be nonlinear. A dose-independent plateau in the dose range from about 50 to 500 mGy was observed, where the level of cytogenetic damage was significantly different from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexity, using the most common quantitative criteria, demonstrated the advantage of a piecewise linear model over linear and polynomial models in approximating the frequency of cytogenetical disturbances. The results of the study support the hypothesis of indirect mechanisms of mutagenesis induced by low doses. Fundamental and applied implications of these findings are discussed.

Characterization of the nanoDot OSLD dosimeter in CT

PubMed Central

Scarboro, Sarah B.; Cody, Dianna; Alvarez, Paola; Followill, David; Court, Laurence; Stingo, Francesco C.; Zhang, Di; Kry, Stephen F.

2015-01-01

Purpose: The extensive use of computed tomography (CT) in diagnostic procedures is accompanied by a growing need for more accurate and patient-specific dosimetry techniques. Optically stimulated luminescent dosimeters (OSLDs) offer a potential solution for patient-specific CT point-based surface dosimetry by measuring air kerma. The purpose of this work was to characterize the OSLD nanoDot for CT dosimetry, quantifying necessary correction factors, and evaluating the uncertainty of these factors. Methods: A characterization of the Landauer OSL nanoDot (Landauer, Inc., Greenwood, IL) was conducted using both measurements and theoretical approaches in a CT environment. The effects of signal depletion, signal fading, dose linearity, and angular dependence were characterized through direct measurement for CT energies (80–140 kV) and delivered doses ranging from ∼5 to >1000 mGy. Energy dependence as a function of scan parameters was evaluated using two independent approaches: direct measurement and a theoretical approach based on Burlin cavity theory and Monte Carlo simulated spectra. This beam-quality dependence was evaluated for a range of CT scanning parameters. Results: Correction factors for the dosimeter response in terms of signal fading, dose linearity, and angular dependence were found to be small for most measurement conditions (<3%). The relative uncertainty was determined for each factor and reported at the two-sigma level. Differences in irradiation geometry (rotational versus static) resulted in a difference in dosimeter signal of 3% on average. Beam quality varied with scan parameters and necessitated the largest correction factor, ranging from 0.80 to 1.15 relative to a calibration performed in air using a 120 kV beam. Good agreement was found between the theoretical and measurement approaches. Conclusions: Correction factors for the measurement of air kerma were generally small for CT dosimetry, although angular effects, and particularly effects due to changes in beam quality, could be more substantial. In particular, it would likely be necessary to account for variations in CT scan parameters and measurement location when performing CT dosimetry using OSLD. PMID:25832070

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

NASA Astrophysics Data System (ADS)

Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

2002-10-01

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients

PubMed Central

Ramos, Alga S; Seip, Richard L; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F; Cadilla, Carmen L; Renta, Jessica Y; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

2012-01-01

Aim This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. Patients & methods A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. Results The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better ‘ideal dose’ estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R2 = 51%). Conclusion Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients. PMID:23215886

Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator.

PubMed

Tran, Jonathan Q; Hartung, Jeffrey P; Peach, Robert J; Boehm, Marcus F; Rosen, Hugh; Smith, Heather; Brooks, Jennifer L; Timony, Gregg A; Olson, Allan D; Gujrathi, Sheila; Frohna, Paul A

2017-08-01

The sphingosine-1-phosphate 1 receptor (S1P 1R ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P 1R and S1P 5R receptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases. This first-in-human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose-escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose-limiting toxicities. The most common ozanimod-related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady-state volume of distribution (73-101 L/kg), moderate oral clearance (204-227 L/h), and an elimination half-life of approximately 17 to 21 hours. Ozanimod produced a robust dose-dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose-dependent negative chronotropic effect was observed following the first dose, with the dose-escalation regimen attenuating the first-dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once-daily regimens under clinical investigation. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single and Multiple Doses of Trandolapril, an Effective Angiotensin-Converting Enzyme Inhibitor, in Healthy Chinese Subjects.

PubMed

Li, Xiaojiao; Liu, Chang; Wu, Min; Zhang, Hong; Sun, Yanfu; Cheng, Longmei; Chen, Hong; Liu, Chengjiao; Yang, Lizhi; Zhang, Qi; Cao, Yuchen; Gu, Jingkai; Ding, Yanhua

2016-08-01

Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor. This study was designed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six men and six women) were randomized into a single-dose, 3 × 3 crossover study (1-2-4 mg, 2-4-1 mg, and 4-1-2 mg), and a multiple-dose study (2 mg/day, 6 days). Serial blood and urine samples were collected after drug administration and analyzed using a validated LC-MS/MS method, and the trandolapril and trandolaprilat PK parameters were obtained. PD was evaluated by the changes in blood pressure and heart rates after dosing. Tolerability was assessed by monitoring adverse events, vital signs, ECGs, and changes in laboratory tests. In the single-dose study, trandolapril was absorbed rapidly, and peak plasma levels (C max, 1.57, 3.77, and 7.99 ng/mL) and AUCs (1.89, 3.46, and 6.47 ng/mL) were dose-dependent. The AUC0-∞ of trandolaprilat was dose-dependent, but in a non-linear fashion. The cumulative urine excretion of trandolapril and trandolaprilat was 5.51, 6.20, and 7.41 % for three doses, respectively. In the multiple-dose study, steady-state pharmacokinetics was observed; there was no trandolapril accumulation, but there was mild trandolaprilat accumulation (R = 1.67). Trandolapril was well tolerated. The most pronounced reductions in blood pressure were observed at 8 h after administration, which was later than T max. No orthostatic hypotension occurred. The pharmacokinetics and pharmacodynamics following single and multiple oral doses trandolapril in healthy Chinese subjects are similar to those observed in non-Chinese healthy subjects.

Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats.

PubMed

Dahan, A; Yassen, A; Bijl, H; Romberg, R; Sarton, E; Teppema, L; Olofsen, E; Danhof, M

2005-06-01

There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal PCO2 of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 microg kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 microg kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial PCO2 was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 microg kg(-1) and fentanyl 0, 50, 68 and 90 microg kg(-1). In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses > or = 2.9 microg kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses > or = 3.0 microg kg(-1) to about 50% of baseline. In rats, the relationship of arterial PCO2 and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum PaCO2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on PaCO2, with a ceiling effect at doses > 1.4 microg kg(-1). The effect on PaCO2 was modest (maximum value measured, 5.5 kPa). Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.

Radiation-Induced Carcinogenesis: Mechanistically Based Differences between Gamma-Rays and Neutrons, and Interactions with DMBA

PubMed Central

Shuryak, Igor; Brenner, David J.; Ullrich, Robert L.

2011-01-01

Different types of ionizing radiation produce different dependences of cancer risk on radiation dose/dose rate. Sparsely ionizing radiation (e.g. γ-rays) generally produces linear or upwardly curving dose responses at low doses, and the risk decreases when the dose rate is reduced (direct dose rate effect). Densely ionizing radiation (e.g. neutrons) often produces downwardly curving dose responses, where the risk initially grows with dose, but eventually stabilizes or decreases. When the dose rate is reduced, the risk increases (inverse dose rate effect). These qualitative differences suggest qualitative differences in carcinogenesis mechanisms. We hypothesize that the dominant mechanism for induction of many solid cancers by sparsely ionizing radiation is initiation of stem cells to a pre-malignant state, but for densely ionizing radiation the dominant mechanism is radiation-bystander-effect mediated promotion of already pre-malignant cell clone growth. Here we present a mathematical model based on these assumptions and test it using data on the incidence of dysplastic growths and tumors in the mammary glands of mice exposed to high or low dose rates of γ-rays and neutrons, either with or without pre-treatment with the chemical carcinogen 7,12-dimethylbenz-alpha-anthracene (DMBA). The model provides a mechanistic and quantitative explanation which is consistent with the data and may provide useful insight into human carcinogenesis. PMID:22194850

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

SU-E-T-611: Effective Treatment Volume of the Small Size IORT Applicators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krechetov, A.S.; ASK Physics, Mountain View, CA; Goer, D.A.

2014-06-01

Purpose Mobile electron linear accelerators are gaining more attention recently, providing a lower cost and simpler way to perform intraoperative treatment. However, the simplicity of the treatment process does not eliminate the need for proper attention to the technical aspects of the treatment. One of the potential pitfalls is incorrect selection of the appropriate applicator size to adequately cover the tumor bed to the prescription dose. When treating tumor beds in the pelvis, the largest applicator that fits into the pelvis is usually selected as there is concern about microscopic extension of the disease along the sidewalls of the pelvis.more » But when treating early stage breast tumors, there is a natural tendency to select an applicator as small as possible so as not to jeopardize cosmesis. Methods This investigation questions how much of the typical breast treatment volume gets adequate exposure and what is the correct strategy in selecting the proper applicator size. Actual data from isodose scans were analyzed. Results We found that typical treatment dose prescriptions can cover as much as 80% and as little as 20% of the nominal treatment volume depending on the applicator size and energy of the beam and whether the dose is prescribed to the 80 or 90% isodose level. Treatment volume is defined as a cylinder with diameter equal to applicator and height equal to the corresponding D80 or D90 depth. Conclusion If mobile linear accelerators are used, there can be significant amount of “cold volume” depending on the applicator size and this should be taken into account when selecting the applicator that is needed. Using too small of an applicator could result in significant under-dosing to the tissue at risk. Long-term clinical data demonstrates that selecting an adequate field size results in good ontological control as well as excellent cosmesis. Intraop Medical Corp was providing facilities and equipment for this research.« less

Gamma radiation effects on seed germination, growth and pigment content, and ESR study of induced free radicals in maize (Zea mays).

PubMed

Marcu, Delia; Damian, Grigore; Cosma, Constantin; Cristea, Victoria

2013-09-01

The effects of gamma radiation are investigated by studying plant germination, growth and development, and biochemical characteristics of maize. Maize dry seeds are exposed to a gamma source at doses ranging from 0.1 to 1 kGy. Our results show that the germination potential, expressed through the final germination percentage and the germination index, as well as the physiological parameters of maize seedlings (root and shoot lengths) decreased by increasing the irradiation dose. Moreover, plants derived from seeds exposed at higher doses (≤0.5 kGy) did not survive more than 10 days. Biochemical differences based on photosynthetic pigment (chlorophyll a, chlorophyll b, carotenoids) content revealed an inversely proportional relationship to doses of exposure. Furthermore, the concentration of chlorophyll a was higher than chlorophyll b in both irradiated and non-irradiated seedlings. Electron spin resonance spectroscopy used to evaluate the amount of free radicals induced by gamma ray treatment demonstrates that the relative concentration of radiation-induced free radicals depends linearly on the absorbed doses.

Luminescence isochron dating: a new approach using different grain sizes.

PubMed

Zhao, H; Li, S H

2002-01-01

A new approach to isochron dating is described using different sizes of quartz and K-feldspar grains. The technique can be applied to sites with time-dependent external dose rates. It is assumed that any underestimation of the equivalent dose (De) using K-feldspar is by a factor F, which is independent of grain size (90-350 microm) for a given sample. Calibration of the beta source for different grain sizes is discussed, and then the sample ages are calculated using the differences between quartz and K-feldspar De from grains of similar size. Two aeolian sediment samples from north-eastern China are used to illustrate the application of the new method. It is confirmed that the observed values of De derived using K-feldspar underestimate the expected doses (based on the quartz De) but, nevertheless, these K-feldspar De values correlate linearly with the calculated internal dose rate contribution, supporting the assumption that the underestimation factor F is independent of grain size. The isochron ages are also compared with the results obtained using quartz De and the measured external dose rates.

Influence of DNA Repair on Nonlinear Dose-Responses for Mutation

PubMed Central

Johnson, George E.

2013-01-01

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O6-methylguanine (O6MeG) by the suicide enzyme O6MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis. PMID:23288051

Influence of DNA repair on nonlinear dose-responses for mutation.

PubMed

Thomas, Adam D; Jenkins, Gareth J S; Kaina, Bernd; Bodger, Owen G; Tomaszowski, Karl-Heinz; Lewis, Paul D; Doak, Shareen H; Johnson, George E

2013-03-01

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.

Species differences in the disposition and metabolism of nalidixic acid.

PubMed

Nomeir, A A; Markham, P; Burka, L T; Griffin, R J; Ghanayem, B I

1996-10-01

Nalidixic acid (NA) is an antimicrobial drug that has been used to treat urinary tract infections. A study of NA by the National Toxicology Program indicated that chronic administration in the diet at doses equivalent to 82 and 175 mg/kg/day for rats, and 175 and 475 mg/kg/day for mice resulted in neoplastic lesions in the preputial and clitoral glands of male and female Fischer 344 rats, respectively, but not in male and female B6C3F1 mice. Our study was designed to evaluate the metabolic basis of this species and tissue-dependent carcinogenicity. [14C]NA was administered by oral gavage as a suspension in corn oil at doses of 20, 200 or 500 mg/kg. Based on urinary excretion data, at least 35 to 46 and 57 to 79% of dose was absorbed from the gastrointestinal tracts of mice and rats, respectively. NA-derived radioactivity was excreted primarily in urine and feces. The urinary and fecal metabolite profiles were species dependent. At 72 hr after administration, in both genders of rats and mice, the highest concentrations of radioactivity were observed in the liver, and the lowest were in the brain and adipose tissue. The preputial and clitoral glands of male and female rats, respectively, contained consistently and substantially higher concentrations of radioactivity compared to all other tissues, with the exception of liver. In mice, the levels of radioactivity in these tissues were near or below quantifiable levels. The metabolism and disposition characteristics of NA were linear in male and female mice over a dose range of 20 to 500 mg/kg: in rats, they were dose dependent. Results of this study suggest that the species- and tissue-dependent differences in carcinogenicity of NA were associated with differences in metabolism and disposition between the two species.

A neutron track etch detector for electron linear accelerators in radiotherapy

PubMed Central

Vukovic, Branko; Faj, Dario; Poje, Marina; Varga, Maja; Radolic, Vanja; Miklavcic, Igor; Ivkovic, Ana; Planinic, Josip

2010-01-01

Background Electron linear accelerators in medical radiotherapy have replaced cobalt and caesium sources of radiation. However, medical accelerators with photon energies over 10 MeV generate undesired fast neutron contamination in a therapeutic X-ray photon beam. Photons with energies above 10 MeV can interact with the atomic nucleus of a high-Z material, of which the target and the head of an accelerator consist, and lead to the neutron ejection. Results and conclusions. Our neutron dosimeter, composed of the LR-115 track etch detector and boron foil BN-1 converter, was calibrated on thermal neutrons generated in the nuclear reactor of the Josef Stefan Institute (Slovenia), and applied to dosimetry of undesirable neutrons in photon radiotherapy by the linear accelerator 15 MV Siemens Mevatron. Having considered a high dependence of a cross-section between neutron and boron on neutron energy, and broad neutron spectrum in a photon beam, as well as outside the entrance door to maze of the Mevatron, we developed a method for determining the effective neutron detector response. A neutron dose rate in the photon beam was measured to be 1.96 Sv/h. Outside the Mevatron room the neutron dose rate was 0.62 μSv/h. PACS: 87.52. Ga; 87.53.St; 29.40.Wk. PMID:22933893

Induction and repair of DNA double-strand breaks in rat cerebellar cortex exposed to 60Co γ-rays

NASA Astrophysics Data System (ADS)

Bulanova, T. S.; Zadneprianetc, M. G.; Ježková, L.; Kruglyakova, E. A.; Smirnova, E. V.; Boreyko, A. V.

2018-01-01

The induction and repair of DNA double-strand breaks are studied using the immunohistochemical staining procedure of paraffin-embedded rat cerebellum tissues after exposure to γ-rays of 60Co. The dose dependence of radiation-induced colocalized γH2AX/53BP1 foci is studied and its linear character is established. It is shown that these foci are efficiently eliminated 24 h after irradiation.

Thermoluminescence Response of Ge-Doped Cylindrical-, Flat- and Photonic Crystal Silica-Fibres to Electron and Photon Radiation

PubMed Central

Entezam, A.; Khandaker, M. U.; Amin, Y. M.; Ung, N. M.; Bradley, D. A.; Maah, J.; Safari, M. J.; Moradi, F.

2016-01-01

Study has been made of the thermoluminescence (TL) response of silica-based Ge-doped cylindrical, flat and photonic crystal fibres (referred to herein as PCF-collapsed) to electron (6, 12 and 20 MeV) and photon (6, 10 MV) irradiation and 1.25 MeV γ-rays, for doses from 0.1 Gy to 100 Gy. The electron and photon irradiations were delivered through use of a Varian Model 2100C linear accelerator located at the University of Malaya Medical Centre and γ-rays delivered from a 60Co irradiator located at the Secondary Standard Dosimetry Laboratory (SSDL), Malaysian Nuclear Agency. Tailor-made to be of various dimensions and dopant concentrations (6–10% Ge), the fibres were observed to provide TL yield linear with radiation dose, reproducibility being within 1–5%, with insensitivity to energy and angular variation. The sensitivity dependency of both detectors with respect to field size follows the dependency of the output factors. For flat fibres exposed to 6 MV X-rays, the 6% Ge-doped fibre provided the greatest TL yield while PCF-collapsed showed a response 2.4 times greater than that of the 6% Ge-doped flat fibres. The response of cylindrical fibres increased with core size. The fibres offer uniform response, high spatial resolution and sensitivity, providing the basis of promising TL systems for radiotherapy applications. PMID:27149115

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate fluctuations were high. Therefore, also for the time scale of the present investigation, cellular effects of radiation are not invariant to the temporal pattern in dose rate. We propose that with high dose rate variation the cells activate less efficiently their DNA damage response than after continuous irradiation.

Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

NASA Technical Reports Server (NTRS)

George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

2009-01-01

Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further investigate the sensitivity differences for low and low high doses, we performed chronic low dose-rate irradiation, and have begun studies with ATM and Nibrin inhibitors and siRNA knockout of these proteins. Results support the conclusion that for the endpoint of simple chromosomal aberrations (translocation or dicentrics), the increased radiation sensitivity of AT cells found at high doses (>1 Gy) does not carry over to low doses or doserates, while NBS cells show increased sensitivity for both high and low dose exposures.

Biological effects and equivalent doses in radiotherapy: A software solution

PubMed Central

Voyant, Cyril; Julian, Daniel; Roustit, Rudy; Biffi, Katia; Lantieri, Céline

2013-01-01

Background The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding delivered doses or any future prescriptions relating to treatment changes. Aim We, therefore, propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). Materials and methods The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. Results and conclusions The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to an equivalent dose computed using standard calculators in seven French radiotherapy centers. PMID:24936319

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

PubMed

Kudryasheva, N S; Rozhko, T V

2015-04-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients.

PubMed

Csajka, Chantal; Crettol, Séverine; Guidi, Monia; Eap, Chin B

2016-12-01

Methadone is a μ-opioid agonist widely used for the treatment of pain, and for detoxification or maintenance treatment in opioid addiction. It has been shown to exhibit large pharmacokinetic variability and concentration-QTc relationships. In this study we investigated the relative influence of genetic polymorphism and other variables on the dose concentration-QTc relationship. A population model for methadone enantiomers in 251 opioid-dependent patients was developed using non-linear mixed effect modeling (NONMEM ® ). Various models were tested to characterize the pharmacokinetics of (R)- and (S)-methadone and the pharmacokinetic-pharmacodynamic relationship, while including demographics, physiological conditions, co-medications, and genetic variants as covariates. Model-based simulations were performed to assess the relative increase in QTc with dose upon stratification according to genetic polymorphisms involved in methadone disposition. A two-compartment model with first-order absorption and lag time provided the best model fit for (R)- and (S)-methadone pharmacokinetics. (S)-methadone clearance was influenced by cytochrome P450 (CYP) 2B6 activity, ABCB1 3435C>T, and α-1 acid glycoprotein level, while (R)-methadone clearance was influenced by CYP2B6 activity, POR*28, and CYP3A4*22. A linear model described the methadone concentration-QTc relationship, with a mean QTc increase of 9.9 ms and 19.2 ms per 1000 ng/ml of (R)- and (S)-methadone, respectively. Simulations with different methadone doses up to 240 mg/day showed that <8 % of patients presented with a QTc interval above 450 ms; however, this might reach 12 to 18 % for (R)- and (S)-methadone, respectively, in patients with a genetic status associated with a decreased methadone elimination at doses exceeding 240 mg/day. Risk factor assessment, electrocardiogram monitoring, and therapeutic drug monitoring are beneficial to optimize treatment in methadone patients, especially for those who have low levels despite high methadone doses, or who are at risk of overdosing.

Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

PubMed

Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

2016-06-01

Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

Non-parametric estimation of low-concentration benzene metabolism.

PubMed

Cox, Louis A; Schnatter, A Robert; Boogaard, Peter J; Banton, Marcy; Ketelslegers, Hans B

2017-12-25

Two apparently contradictory findings in the literature on low-dose human metabolism of benzene are as follows. First, metabolism is approximately linear at low concentrations, e.g., below 10 ppm. This is consistent with decades of quantitative modeling of benzene pharmacokinetics and dose-dependent metabolism. Second, measured benzene exposure and metabolite concentrations for occupationally exposed benzene workers in Tianjin, China show that dose-specific metabolism (DSM) ratios of metabolite concentrations per ppm of benzene in air decrease steadily with benzene concentration, with the steepest decreases below 3 ppm. This has been interpreted as indicating that metabolism at low concentrations of benzene is highly nonlinear. We reexamine the data using non-parametric methods. Our main conclusion is that both findings are correct; they are not contradictory. Low-concentration metabolism can be linear, with metabolite concentrations proportional to benzene concentrations in air, and yet DSM ratios can still decrease with benzene concentrations. This is because a ratio of random variables can be negatively correlated with its own denominator even if the mean of the numerator is proportional to the denominator. Interpreting DSM ratios that decrease with air benzene concentrations as evidence of nonlinear metabolism is therefore unwarranted when plots of metabolite concentrations against benzene ppm in air show approximately straight-line relationships between them, as in the Tianjin data. Thus, an apparent contradiction that has fueled heated discussions in the recent literature can be resolved by recognizing that highly nonlinear, decreasing DSM ratios are consistent with linear metabolism. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of ractopamine hydrochloride (Optaflexx) dose and duration on growth performance and carcass characteristics of finishing steers.

PubMed

Bittner, C J; Crawford, G I; Berger, L L; Holt, S; Pritchard, R R; Platter, W J; Van Koevering, M T; Pyatt, N A; Erickson, G E

2016-12-01

Three experiments evaluated the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of feedlot steers. In total, 1,509 crossbred steers (530 kg initial BW [SD 22]) were used in a randomized complete block design using a 3 × 3 factorial treatment structure. Treatments consisted of RAC dose (0, 100, or 200 mg/steer daily) and duration (28, 35, or 42 d) of RAC feeding prior to harvest. Initiation of RAC dose was staggered (7 d apart) based on RAC duration, which resulted in common days on feed among treatments. Data from the 3 experiments were combined for statistical analyses. There were no RAC dose × duration interactions ( ≥ 0.85) for growth performance. Live final BW was not different ( ≥ 0.24) as RAC dose increased. Dry matter intake linearly decreased ( < 0.01) as RAC dose increased. Live ADG and G:F linearly increased ( ≤ 0.01) as RAC dose increased. Carcass-adjusted ADG and G:F linearly increased ( ≤ 0.02) as RAC dose increased. Compared with steers fed 0 mg RAC/steer daily, G:F was improved by 5.0 and 13.0% when steers were fed 100 ( = 0.31) and 200 ( = 0.01) mg RAC/steer daily, respectively. Hot carcass weight tended ( = 0.10) to linearly increase as RAC dose increased, with carcasses from steers fed 100 ( = 0.38) and 200 ( = 0.10) mg RAC/steer daily being 2.2 and 4.1 kg heavier, respectively, than carcasses from steers fed 0 mg RAC/steer daily. Increasing RAC dose linearly ( < 0.01) increased LM area and linearly ( = 0.02) decreased marbling score. Live final BW was not different ( ≥ 0.60) among RAC durations. Carcass-adjusted final BW, ADG, and G:F were not different ( ≥ 0.41) as RAC duration increased. Carcass traits did not differ ( ≥ 0.18) among RAC duration. Feeding 200 mg RAC/steer daily improved ADG, feed efficiency, and HCW. Increasing the feeding duration of RAC had no effect of growth performance or carcass characteristics. These data indicate that feeding 200 mg RAC/steer daily for 28 d improves steer growth performance.

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

The ambient dose equivalent at flight altitudes: a fit to a large set of data using a Bayesian approach.

PubMed

Wissmann, F; Reginatto, M; Möller, T

2010-09-01

The problem of finding a simple, generally applicable description of worldwide measured ambient dose equivalent rates at aviation altitudes between 8 and 12 km is difficult to solve due to the large variety of functional forms and parametrisations that are possible. We present an approach that uses Bayesian statistics and Monte Carlo methods to fit mathematical models to a large set of data and to compare the different models. About 2500 data points measured in the periods 1997-1999 and 2003-2006 were used. Since the data cover wide ranges of barometric altitude, vertical cut-off rigidity and phases in the solar cycle 23, we developed functions which depend on these three variables. Whereas the dependence on the vertical cut-off rigidity is described by an exponential, the dependences on barometric altitude and solar activity may be approximated by linear functions in the ranges under consideration. Therefore, a simple Taylor expansion was used to define different models and to investigate the relevance of the different expansion coefficients. With the method presented here, it is possible to obtain probability distributions for each expansion coefficient and thus to extract reliable uncertainties even for the dose rate evaluated. The resulting function agrees well with new measurements made at fixed geographic positions and during long haul flights covering a wide range of latitudes.

Retrieving atmospheric transmissivity for biologically active daily dose, in various european sites

NASA Astrophysics Data System (ADS)

de La Casinière, A.; Touré, M. L.; Lenoble, J.; Cabot, T.

2003-04-01

In the frame of the European Project EDUCE, global UV irradiance spectra recorded all along the year in several European sites are stored in a common database located in Finland. From the spectra set of some of these stations, are calculated atmospheric transmissivities for daily doses of four biologically active UV radiation, namely: UV-B, erythema, DNA damage, and plant damage. A transmissivity is defined as the ratio of the ground level value of the daily dose of interest to its corresponding extra-atmospheric value. Multiple linear correlation of the various transmissivities with three predictors (daily sunshine fraction, cosine of the daily minimum SZA, and daily total ozone column) assumed to be independent variables, are done for year 2000. The coefficients obtained from year 2000 correlation in a given site are expected to retrieve, from the local predictors, the daily dose for year 2001 in the same site, the average error being lesser than 10% for monthly mean values, and lesser than 5% for three-monthly mean values, depending on the daily dose type. Comparison of yearly mean daily doses retrieved in a given site from coefficients obtained in other sites is also presented.

Introduction to methodology of dose-response meta-analysis for binary outcome: With application on software.

PubMed

Zhang, Chao; Jia, Pengli; Yu, Liu; Xu, Chang

2018-05-01

Dose-response meta-analysis (DRMA) is widely applied to investigate the dose-specific relationship between independent and dependent variables. Such methods have been in use for over 30 years and are increasingly employed in healthcare and clinical decision-making. In this article, we give an overview of the methodology used in DRMA. We summarize the commonly used regression model and the pooled method in DRMA. We also use an example to illustrate how to employ a DRMA by these methods. Five regression models, linear regression, piecewise regression, natural polynomial regression, fractional polynomial regression, and restricted cubic spline regression, were illustrated in this article to fit the dose-response relationship. And two types of pooling approaches, that is, one-stage approach and two-stage approach are illustrated to pool the dose-response relationship across studies. The example showed similar results among these models. Several dose-response meta-analysis methods can be used for investigating the relationship between exposure level and the risk of an outcome. However the methodology of DRMA still needs to be improved. © 2018 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Radiation response of industrial materials: Dose-rate and morphology implications

NASA Astrophysics Data System (ADS)

Berejka, Anthony J.

2007-08-01

Industrial uses of ionizing radiation mostly rely upon high current, high dose-rate (100 kGy/s) electron beam (EB) accelerators. To a lesser extent, industry uses low dose-rate (2.8 × 10-3 kGy/s) radioactive Cobalt-60 as a gamma source, generally for some rather specific purposes, as medical device sterilization and the treatment of food and foodstuffs. There are nearly nine times as many (∼1400) high current EB units in commercial operation than gamma sources (∼160). However, gamma sources can be easily scaled-down so that much research on materials effects is conducted using gamma radiation. Likewise, laboratories are more likely to have very low beam current and consequently low dose-rate accelerators such as Van de Graaff generators and linear accelerators. With the advent of very high current EB accelerators, X-ray processing has become an industrially viable option. With X-rays from high power sources, dose-rates can be modulated based upon accelerator power and the attenuation of the X-ray by the distance of the material from the X-ray target. Dose and dose-rate dependence has been found to be of consequence in several commercial applications which can employ the use of ionizing radiation. The combination of dose and dose-rate dependence of the polymerization and crosslinking of wood impregnants and of fiber composite matrix materials can yield more economically viable results which have promising commercial potential. Monomer and oligomer structure also play an important role in attaining these desirable results. The influence of morphology is shown on the radiation response of olefin polymers, such as ethylene, propylene and isobutylene polymers and their copolymers. Both controlled morphology and controlled dose-rate have commercial consequences. These are also impacted both by the adroit selection of materials and through the possible use of X-ray processing.

Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siva, Shankar, E-mail: shankar.siva@petermac.org; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville; Hardcastle, Nicholas

2015-10-01

Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation andmore » perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.« less

Interplay effect on a 6-MV flattening-filter-free linear accelerator with high dose rate and fast multi-leaf collimator motion treating breast and lung phantoms.

PubMed

Netherton, Tucker; Li, Yuting; Nitsch, Paige; Shaitelman, Simona; Balter, Peter; Gao, Song; Klopp, Ann; Muruganandham, Manickam; Court, Laurence

2018-06-01

Using a new linear accelerator with high dose rate (800 MU/min), fast MLC motions (5.0 cm/s), fast gantry rotation (15 s/rotation), and 1 cm wide MLCs, we aimed to quantify the effects of complexity, arc number, and fractionation on interplay for breast and lung treatments under target motion. To study lung interplay, eight VMAT plans (1-6 arcs) and four-nine-field sliding-window IMRT plans varying in complexity were created. For the breast plans, four-four-field sliding-window IMRT plans were created. Using the Halcyon 1.0 linear accelerator, each plan was delivered five times each under sinusoidal breathing motion to a phantom with 20 implanted MOSFET detectors; MOSFET dose (cGy), delivery time, and MU/cGy values were recorded. Maximum and mean dose deviations were calculated from MOSFET data. The number of MOSFETs with at least 19 of 20 detectors agreeing with their expected dose within 5% per fraction was calculated across 10 6 iterations to model dose deviation as function of fraction number for all plan variants. To put interplay plans into clinical context, additional IMRT and VMAT plans were created and delivered for the sites of head and neck, prostate, whole brain, breast, pelvis, and lung. Average modulation and interplay effect were compared to those from conventional linear accelerators, as reported from previous studies. The mean beam modulation for plans created for the Halcyon 1.0 linear accelerator was 2.9 MU/cGy (two- to four-field IMRT breast plans), 6.2 MU/cGy (at least five-field IMRT), and 3.6 MU/cGy (four-arc VMAT). To achieve treatment plan objectives, Halcyon 1.0 VMAT plans require more arcs and modulation than VMAT on conventional linear accelerators. Maximum and mean dose deviations increased with increasing plan complexity under tumor motion for breast and lung treatments. Concerning VMAT plans under motion, maximum, and mean dose deviations were higher for one arc than for two arcs regardless of plan complexity. For plan variants with maximum dose deviations greater than 3.7%, dose deviation as a function of fraction number was protracted. For treatments on the Halcyon 1.0 linear accelerator, the convergence of dose deviation with fraction number happened more slowly than reported for conventional linear accelerators. However, if plan complexity is reduced for IMRT and if tumor motion is less than ~10-mm, interplay is greatly reduced. To minimize dose deviations across multiple fractions for dynamic targets, we recommend limiting treatment plan complexity and avoiding one-arc VMAT on the Halcyon 1.0 linear accelerator when interplay is a concern. © 2018 American Association of Physicists in Medicine.

Increased prandial insulin secretion after administration of a single preprandial oral dose of repaglinide in patients with type 2 diabetes.

PubMed

Owens, D R; Luzio, S D; Ismail, I; Bayer, T

2000-04-01

To examine the dose-related pharmacodynamics and pharmacokinetics of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind randomized cross-over studies. Patients were randomized to receive a single oral dose of repaglinide (0.5, 1.0, and 2.0 mg in study 1 and 4.0 mg in study 2) or placebo (both studies) administered 15 min before the first of two sequential identical standard meals (breakfast and lunch) that were 4 h apart. During each of the study days, which were 1 week apart, blood samples were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose, insulin, C-peptide, and repaglinide concentrations. During the first meal period (0-240 min), administration of repaglinide reduced significantly the area under the curve (AUC) for glucose concentration and significantly increased the AUC for insulin levels, C-peptide levels, and the insulin secretion rate. These results, compared with those of administering placebo, were dose dependent and log linear. The effect of repaglinide administration on insulin secretion was most pronounced in the early prandial period. Within 30 min, it caused a relative increase in insulin secretion of up to 150%. During the second meal period (240-480 min), there was no difference between repaglinide and placebo administration in the AUC for glucose concentration, C-peptide concentration, and the estimated insulin secretion rate. A single dose of repaglinide (0.5-4.0 mg) before breakfast improves insulin secretion and reduces prandial hyperglycemia dose-dependently Administration of repaglinide had no effect on insulin secretion with the second meal, which was consumed 4 h after breakfast.

Do technological advances in linear accelerators improve dosimetric outcomes in stereotaxy? A head-on comparison of seven linear accelerators using volumetric modulated arc therapy-based stereotactic planning.

PubMed

Sarkar, B; Pradhan, A; Munshi, A

2016-01-01

Linear accelerator (Linac) based stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using volumetric modulated arc therapy (VMAT) has been used for treating small intracranial lesions. Recent development in the Linacs such as inbuilt micro multileaf collimator (MLC) and flattening filter free (FFF) beam are intended to provide a better dose conformity and faster delivery when using VMAT technique. This study was aimed to compare the dosimetric outcomes and monitor units (MUs) of the stereotactic treatment plans for different commercially available MLC models and beam profiles. Ten patients having 12 planning target volume (PTV)/gross target volume's (GTVs) who received the SRS/SRT treatment in our clinic using Axesse Linac (considered reference arm gold standard) were considered for this study. The test arms comprised of plans using Elekta Agility with FFF, Elekta Agility with the plane beam, Elekta APEX, Varian Millennium 120, Varian Millennium 120HD, and Elekta Synergy in Monaco treatment planning system. Planning constraints and calculation grid spacing were not altered in the test plans. To objectively evaluate the efficacy of MLC-beam model, the resultant dosimetric outcomes were subtracted from the reference arm parameters. V95%, V100%, V105%, D1%, maximum dose, and mean dose of PTV/GTV showed a maximum inter MLC - beam model variation of 1.5% and 2% for PTV and GTV, respectively. Average PTV conformity index and heterogeneity index shows a variation in the range 0.56-0.63 and 1.08-1.11, respectively. Mean dose difference (excluding Axesse) for all organs varied between 1.1 cGy and 74.8 cGy (mean dose = 6.1 cGy standard deviation [SD] = 26.9 cGy) and 1.7 cGy-194.5 cGy (mean dose 16.1 cGy SD = 57.2 cGy) for single and multiple fraction, respectively. The dosimetry of VMAT-based SRS/SRT treatment plan had minimal dependence on MLC and beam model variations. All tested MLC and beam model could fulfil the desired PTV coverage and organs at risk dose constraints. The only notable difference was the halving of the MU for FFF beam as compared to the plane beam. This has the potential to reduce the total patient on couch time by 15% (approximately 2 min).

Linear energy transfer incorporated intensity modulated proton therapy optimization

NASA Astrophysics Data System (ADS)

Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

The pharmacokinetics of a new benzamide drug clebopride, in the rat and the dog.

PubMed

Segura, J; García, I; Borja, L; Tarrús, E; Bakke, O M

1981-04-01

After intravenous, intramuscular and oral administration of clebopride in the rat and the dog its apparent volume of distribution is high (1.6-3.2 1 kg-1) and it has a longer biological half-life than metoclopramide in both species. High clearance values and concentrations of metabolites in plasma after oral administration indicate that the drug is subjected to an extensive first pass metabolism in the rat. Thus, clebopride administered orally gives relatively low concentrations in the systemic circulation in rats even though it is rapidly absorbed. The metabolic processes appear to become saturated at high doses which is reflected in dose-dependent kinetics. Linear kinetics were observed in the dog, although enterohepatic recycling could occur.

Total Dose Effects on Single Event Transients in Digital CMOS and Linear Bipolar Circuits

NASA Technical Reports Server (NTRS)

Buchner, S.; McMorrow, D.; Sibley, M.; Eaton, P.; Mavis, D.; Dusseau, L.; Roche, N. J-H.; Bernard, M.

2009-01-01

This presentation discusses the effects of ionizing radiation on single event transients (SETs) in circuits. The exposure of integrated circuits to ionizing radiation changes electrical parameters. The total ionizing dose effect is observed in both complementary metal-oxide-semiconductor (CMOS) and bipolar circuits. In bipolar circuits, transistors exhibit grain degradation, while in CMOS circuits, transistors exhibit threshold voltage shifts. Changes in electrical parameters can cause changes in single event upset(SEU)/SET rates. Depending on the effect, the rates may increase or decrease. Therefore, measures taken for SEU/SET mitigation might work at the beginning of a mission but not at the end following TID exposure. The effect of TID on SET rates should be considered if SETs cannot be tolerated.

Investigation of dosimetric characteristics of a core-shell quantum dots nano composite (CdTe/CdS/PMMA): fabrication of a new gamma sensor

NASA Astrophysics Data System (ADS)

Feizi, Shahzad; Zare, Hakimeh; Hoseinpour, Masoumeh

2018-06-01

CdTe/CdS-PMMA nanocomposite was prepared using dispersion of CdTe/CdS core-shell quantum dots (QDs) in poly methyl methacrylate (PMMA) polymer matrix. High-quality CdTe/CdS core/shell quantum dots were synthesized in aqueous solution and were transferred from water to chloroform using ligand-exchange process in the presence of 1-dodecanethiol (1-DDT). Transmission electron microscopy analysis reveals that the obtained nano-particles are highly crystalline nature with mean diameter of 3.6 nm. To prepare an ohmic contact detector, a conductive cell with two silver coated walls was designed and fabricated for exploring gamma detecting properties of the nano composite. New detector was assessed for the linearity of doserate response, angular dependence, sensitivity and repeatability. The results show that the dose rate response of the prepared sensor is linear in the dose rate range of 50-145 mGy/min. So this nanocomposite can be utilized as a potential gamma sensor in the medical radiation device design.

Method for simulating dose reduction in digital mammography using the Anscombe transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borges, Lucas R., E-mail: lucas.rodrigues.borges@usp.br; Oliveira, Helder C. R. de; Nunes, Polyana F.

2016-06-15

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtainedmore » by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

PubMed Central

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2016-01-01

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID:27277017

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saur, Sigrun; Frengen, Jomar; Department of Oncology and Radiotherapy, St. Olavs University Hospital, N-7006 Trondheim

Film dosimetry using radiochromic EBT film in combination with a flatbed charge coupled device scanner is a useful method both for two-dimensional verification of intensity-modulated radiation treatment plans and for general quality assurance of treatment planning systems and linear accelerators. Unfortunately, the response over the scanner area is nonuniform, and when not corrected for, this results in a systematic error in the measured dose which is both dose and position dependent. In this study a novel method for background correction is presented. The method is based on the subtraction of a correction matrix, a matrix that is based on scansmore » of films that are irradiated to nine dose levels in the range 0.08-2.93 Gy. Because the response of the film is dependent on the film's orientation with respect to the scanner, correction matrices for both landscape oriented and portrait oriented scans were made. In addition to the background correction method, a full dose uncertainty analysis of the film dosimetry procedure was performed. This analysis takes into account the fit uncertainty of the calibration curve, the variation in response for different film sheets, the nonuniformity after background correction, and the noise in the scanned films. The film analysis was performed for film pieces of size 16x16 cm, all with the same lot number, and all irradiations were done perpendicular onto the films. The results show that the 2-sigma dose uncertainty at 2 Gy is about 5% and 3.5% for landscape and portrait scans, respectively. The uncertainty gradually increases as the dose decreases, but at 1 Gy the 2-sigma dose uncertainty is still as good as 6% and 4% for landscape and portrait scans, respectively. The study shows that film dosimetry using GafChromic EBT film, an Epson Expression 1680 Professional scanner and a dedicated background correction technique gives precise and accurate results. For the purpose of dosimetric verification, the calculated dose distribution can be compared with the film-measured dose distribution using a dose constraint of 4% (relative to the measured dose) for doses between 1 and 3 Gy. At lower doses, the dose constraint must be relaxed.« less

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGurk, R; Green, R; Lawrence, M

2015-06-15

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

PubMed

Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

2017-02-01

To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

MCNP-based computational model for the Leksell gamma knife.

PubMed

Trnka, Jiri; Novotny, Josef; Kluson, Jaroslav

2007-01-01

We have focused on the usage of MCNP code for calculation of Gamma Knife radiation field parameters with a homogenous polystyrene phantom. We have investigated several parameters of the Leksell Gamma Knife radiation field and compared the results with other studies based on EGS4 and PENELOPE code as well as the Leksell Gamma Knife treatment planning system Leksell GammaPlan (LGP). The current model describes all 201 radiation beams together and simulates all the sources in the same time. Within each beam, it considers the technical construction of the source, the source holder, collimator system, the spherical phantom, and surrounding material. We have calculated output factors for various sizes of scoring volumes, relative dose distributions along basic planes including linear dose profiles, integral doses in various volumes, and differential dose volume histograms. All the parameters have been calculated for each collimator size and for the isocentric configuration of the phantom. We have found the calculated output factors to be in agreement with other authors' works except the case of 4 mm collimator size, where averaging over the scoring volume and statistical uncertainties strongly influences the calculated results. In general, all the results are dependent on the choice of the scoring volume. The calculated linear dose profiles and relative dose distributions also match independent studies and the Leksell GammaPlan, but care must be taken about the fluctuations within the plateau, which can influence the normalization, and accuracy in determining the isocenter position, which is important for comparing different dose profiles. The calculated differential dose volume histograms and integral doses have been compared with data provided by the Leksell GammaPlan. The dose volume histograms are in good agreement as well as integral doses calculated in small calculation matrix volumes. However, deviations in integral doses up to 50% can be observed for large volumes such as for the total skull volume. The differences observed in treatment of scattered radiation between the MC method and the LGP may be important in this case. We have also studied the influence of differential direction sampling of primary photons and have found that, due to the anisotropic sampling, doses around the isocenter deviate from each other by up to 6%. With caution about the details of the calculation settings, it is possible to employ the MCNP Monte Carlo code for independent verification of the Leksell Gamma Knife radiation field properties.

The risk equivalent of an exposure to-, versus a dose of radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, V.P.

The long-term potential carcinogenic effects of low-level exposure (LLE) are addressed. The principal point discussed is linear, no-threshold dose-response curve. That the linear no-threshold, or proportional relationship is widely used is seen in the way in which the values for cancer risk coefficients are expressed - in terms of new cases, per million persons exposed, per year, per unit exposure or dose. This implies that the underlying relationship is proportional, i.e., ''linear, without threshold''. 12 refs., 9 figs., 1 tab.

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Emergency EPR and OSL dosimetry with table vitamins and minerals.

PubMed

Sholom, S; McKeever, S W S

2016-12-01

Several table vitamins, minerals and L-lysine amino acid have been preliminarily tested as potential emergency dosemeters using electron paramagnetic resonance (EPR) and optically stimulated luminescence (OSL) techniques. Radiation-induced EPR signals were detected in samples of vitamin B2 and L-lysine while samples of multivitamins of different brands as well as mineral Mg demonstrated prominent OSL signals after exposure to ionizing radiation doses. Basic dosimetric properties of the radiation-sensitive substances were studied, namely dose response, fading of the EPR or OSL signals and values of minimum measurable doses (MMDs). For EPR-sensitive samples, the EPR signal is converted into units of dose using a linear dose response and correcting for fading using the measured fading dependence. For OSL-sensitive materials, a multi-aliquot, enhanced-temperature protocol was developed to avoid the problem of sample sensitization and to minimize the influence of signal fading. The sample dose in this case is also evaluated using the dose response and fading curves. MMDs of the EPR-sensitive samples were below 2 Gy while those of the OSL-sensitive materials were below 500 mGy as long as the samples are analyzed within 1 week after exposure. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, H; Jing, J; Xie, C

Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results:more » The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.« less

Regional radiation dose susceptibility within the parotid gland: Effects on salivary loss and recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Haley, E-mail: hdclark@phas.ubc.ca; Reinsberg, Stefan; Hovan, Allan

2015-04-15

Purpose: Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study. Methods: Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman’s rank correlation coefficients, local linear regression) and parametric (least-summore » of squares, least-median of squares) techniques. Results: Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (D{sub L},  45 Gy) + min (D{sub R},  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A{sub 3m} = 0.0604 Gy{sup −1} and A{sub 1y} = 0.0379 Gy{sup −1}. Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose–response dimorphism were observed. Conclusions: Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a population’s mean recovery will exceed 20%–30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.« less

Pigmentation after single and multiple UV-exposures depending on UV-spectrum.

PubMed

Ravnbak, M H; Wulf, H C

2007-04-01

Minimal pigmentation dose (MMD) after a single UV-exposure is well investigated. Whereas only few studies have established MMD after multiple UV-exposures and mainly in fair-skinned persons. The purpose of this study was to establish MMD 1 week after, respectively, one and five UV-exposures in volunteers with a large variation in constitutive pigmentation. A total of 52 volunteers (skin Types II-V) had skin pigmentation quantified by reflectance spectroscopy. They were UV-exposed on the back for 1 and 5 days using a Solar Simulator, narrowband UVB, broadband UVA and UVA1. For all sources a higher dose was needed the more pigmented the skin, except for UVA1. After one UV-exposure, we found a significant positive linear correlation between UV-dose to one MMD, skin type and pre-exposure skin pigmentation. After five UV-exposures the positive linear correlation between UV-dose and MMD and skin type was only significant for narrow band UVB, pre-exposure skin pigmentation was significant also for Solar Simulator. For UVA and particularly UVA1 the MMD was independent of pre-exposure pigmentation. The number of SED to MMD is therefore almost the same for very fair-skinned and dark-skinned persons. Pre-exposure pigmentation was clearly more predictive of MMD than skin type. 50% of MMD equals a pigmentation increase of 1%. The shorter the wavelengths the higher the SED to produce MMD. Solar was the least melanogenic and UVA1 the most melanogenic. For the UVB-sources a higher dose was needed the more pigmented the skin. For UVA the MMD was independent of pre-exposure pigmentation.

Quality assurance in proton beam therapy using a plastic scintillator and a commercially available digital camera.

PubMed

Almurayshid, Mansour; Helo, Yusuf; Kacperek, Andrzej; Griffiths, Jennifer; Hebden, Jem; Gibson, Adam

2017-09-01

In this article, we evaluate a plastic scintillation detector system for quality assurance in proton therapy using a BC-408 plastic scintillator, a commercial camera, and a computer. The basic characteristics of the system were assessed in a series of proton irradiations. The reproducibility and response to changes of dose, dose-rate, and proton energy were determined. Photographs of the scintillation light distributions were acquired, and compared with Geant4 Monte Carlo simulations and with depth-dose curves measured with an ionization chamber. A quenching effect was observed at the Bragg peak of the 60 MeV proton beam where less light was produced than expected. We developed an approach using Birks equation to correct for this quenching. We simulated the linear energy transfer (LET) as a function of depth in Geant4 and found Birks constant by comparing the calculated LET and measured scintillation light distribution. We then used the derived value of Birks constant to correct the measured scintillation light distribution for quenching using Geant4. The corrected light output from the scintillator increased linearly with dose. The system is stable and offers short-term reproducibility to within 0.80%. No dose rate dependency was observed in this work. This approach offers an effective way to correct for quenching, and could provide a method for rapid, convenient, routine quality assurance for clinical proton beams. Furthermore, the system has the advantage of providing 2D visualization of individual radiation fields, with potential application for quality assurance of complex, time-varying fields. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Evaluation of Effective Sources in Uncertainty Measurements of Personal Dosimetry by a Harshaw TLD System

PubMed Central

Hosseini Pooya, SM; Orouji, T

2014-01-01

Background: The accurate results of the individual doses in personal dosimety which are reported by the service providers in personal dosimetry are very important. There are national / international criteria for acceptable dosimetry system performance. Objective: In this research, the sources of uncertainties are identified, measured and calculated in a personal dosimetry system by TLD. Method: These sources are included; inhomogeneity of TLDs sensitivity, variability of TLD readings due to limited sensitivity and background, energy dependence, directional dependence, non-linearity of the response, fading, dependent on ambient temperature / humidity and calibration errors, which may affect on the dose responses. Some parameters which influence on the above sources of uncertainty are studied for Harshaw TLD-100 cards dosimeters as well as the hot gas Harshaw 6600 TLD reader system. Results: The individual uncertainties of each sources was measured less than 6.7% in 68% confidence level. The total uncertainty was calculated 17.5% with 95% confidence level. Conclusion: The TLD-100 personal dosimeters as well as the Harshaw TLD-100 reader 6600 system show the total uncertainty value which is less than that of admissible value of 42% for personal dosimetry services. PMID:25505769

Analysis of peripheral doses for base of tongue treatment by linear accelerator and helical TomoTherapy IMRT

PubMed Central

Lamba, Michael A. S.; Elson, Howard R.

2010-01-01

The purpose of this study was to compare the peripheral doses to various organs from a typical head and neck intensity‐modulated radiation therapy (IMRT) treatment delivered by linear accelerator (linac) and helical TomoTherapy. Multiple human CT data sets were used to segment critical structures and organs at risk, fused and adjusted to an anthropomorphic phantom. Eighteen contours were designated for thermoluminescent dosimeter (TLD) placement. Following the RTOG IMRT Protocol 0522, treatment of the primary tumor and involved nodes (PTV70) and subclinical disease sites (PTV56) was planned utilizing IMRT to 70 Gy and 56 Gy. Clinically acceptable treatment plans were produced for linac and TomoTherapy treatments. TLDs were placed and each treatment plan was delivered to the anthropomorphic phantom four times. Within 2.5 cm (one helical TomoTherapy field width) superior and inferior to the field edges, normal tissue doses were on average 45% lower using linear accelerator. Beyond 2.5 cm, the helical TomoTherapy normal tissue dose was an average of 52% lower. The majority of points proved to be statistically different using the Student's t‐test with p<0.05. Using one method of calculation, probability of a secondary malignancy was 5.88% for the linear accelerator and 4.08% for helical TomoTherapy. Helical TomoTherapy delivers more dose than a linac immediately above and below the treatment field, contributing to the higher peripheral doses adjacent to the field. At distances beyond one field width (where leakage is dominant), helical TomoTherapy doses are lower than linear accelerator doses. PACS number: 87.50.cm Dosimetry/exposure assessment

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

PubMed

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 approximately 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.

Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorissen, BL; Giantsoudi, D; Unkelbach, J

Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less

A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis.

PubMed

Moustafa, Moustafa; Lehrner, Lawrence; Al-Saghir, Fahd; Smith, Mark; Goyal, Sunita; Dillon, Maureen; Hunter, John; Holmes-Farley, Randy

2014-01-01

Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer. Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo, as had been demonstrated in vitro.

Proposed linear energy transfer areal detector for protons using radiochromic film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Rulon; Lin, Liyong; Fager, Marcus

2015-04-15

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured atmore » a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.« less

Genetic Correlation with the DNA Repair Assay in Mice Exposed to High-LET

NASA Technical Reports Server (NTRS)

Penninckx, Sebastien; Ray, Shayoni; Degorre, Charlotte; Guiet, Elodie; Viger, Louise; Pluth, Janice; Snijders, Antoine; Mao, Jian-Hua; Costes, Sylvain V.

2017-01-01

We hypothesize that DNA damage induced by high local energy deposition, occurring when cells are traversed by high-LET (Linear Energy Transfer) particles, can be experimentally modeled by exposing cells to high doses of low-LET. In this work, we validate such hypothesis by characterizing and correlating the time dependence of 53BP1 radiation-induced foci (RIF) for various doses and LET across 72 primary skin fibroblast from mice. This genetically diverse population allows us to understand how genetic may modulate the dose and LET relationship. The cohort was made on average from 3 males and 3 females belonging to 15 different strains of mice with various genetic backgrounds, including the collaborative cross (CC) genetic model (10 strains) and 5 reference mice strains. Cells were exposed to two fluences of three HZE (High Atomic Energy) particles (Si 350 megaelectronvolts per nucleon, Ar 350 megaelectronvolts per nucleon and Fe 600 megaelectronvolts per nucleon) and to 0.1, 1 and 4 grays from a 160 kilovolt X-ray. Individual radiation sensitivity was investigated by high throughput measurements of DNA repair kinetics for different doses of each radiation type. The 53BP1 RIF dose response to high-LET particles showed a linear dependency that matched the expected number of tracks per cell, clearly illustrating the fact that close-by DNA double strand breaks along tracks cluster within one single RIF. By comparing the slope of the high-LET dose curve to the expected number of tracks per cell we computed the number of remaining unrepaired tracks as a function of time post-irradiation. Results show that the percentage of unrepaired track over a 48 hours follow-up is higher as the LET increases across all strains. We also observe a strong correlation between the high dose repair kinetics following exposure to 160 kilovolts X-ray and the repair kinetics of high-LET tracks, with higher correlation with higher LET. At the in-vivo level for the 10-CC strains, we observe that drops in the number of T-cells and B-cells found in the blood of mice 24 hours after exposure to 0.1 gray of 320 kilovolts X-ray correlate well with slower DNA repair kinetics in skin cells exposed to X-ray. Overall, our results suggest that repair kinetics found in skin is a surrogate marker for in-vivo radiation sensitivity in other tissue, such as blood cells, and that such response is modulated by genetic variability.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

PubMed Central

Shuryak, Igor; Loucas, Bradford D.; Cornforth, Michael N.

2017-01-01

Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one) large dose(s) per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ) formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts) exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions). This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction. PMID:29312888

Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

PubMed

Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence

2015-02-01

Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. © 2014, The American College of Clinical Pharmacology.

IS THE DOSE-RESPONSE LINEAR OR NONLINEAR FOR GENOTOXIC EFFECTS?

EPA Science Inventory

IS THE DOSE-RESPONSE LINEAR OR NONLINEAR FOR GENOTOXIC EFFECTS?
Preston, RJ. Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

For considerations of cancer risk assessment from exposure to environmenta...

Thermoluminescence responses of photon- and electron-irradiated lithium potassium borate co-doped with Cu+Mg or Ti+Mg.

PubMed

Alajerami, Y S M; Hashim, S; Ramli, A T; Saleh, M A; Saripan, M I; Alzimami, K; Min Ung, Ngie

2013-08-01

New glasses Li2CO3-K2CO3-H3BO3 (LKB) co-doped with CuO and MgO, or with TiO2 and MgO, were synthesized by the chemical quenching technique. The thermoluminescence (TL) responses of LKB:Cu,Mg and LKB:Ti,Mg irradiated with 6 MV photons or 6 MeV electrons were compared in the dose range 0.5-4.0 Gy. The standard commercial dosimeter LiF:Mg,Ti (TLD-100) was used to calibrate the TL reader and as a reference in comparison of the TL properties of the new materials. The dependence of the responses of the new materials on (60)Co dose is linear in the range of 1-1000 Gy. The TL yields of both of the co-doped glasses and TLD-100 are greater for electron irradiation than for photon irradiation. The TL sensitivity of LKB:Ti,Mg is 1.3 times higher than the sensitivity of LKB:Cu,Mg and 12 times less than the sensitivity of TLD-100. The new TL dosimetric materials have low effective atomic numbers, good linearity of the dose responses, excellent signal reproducibility, and a simple glow curve structure. This combination of properties makes them suitable for radiation dosimetry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mutagenic effects of heavy ion radiation in plants

NASA Technical Reports Server (NTRS)

Mei, M.; Deng, H.; Lu, Y.; Zhuang, C.; Liu, Z.; Qiu, Q.; Qiu, Y.; Yang, T. C.

1994-01-01

Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high Linear Energy Transfer (LET) heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. Restriction-fragment-length-polymorphism (RFLP) analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.

Radiation dosimetry measurements with real time radiation monitoring device (RRMD)-II in Space Shuttle STS-79

NASA Technical Reports Server (NTRS)

Sakaguchi, T.; Doke, T.; Hayashi, T.; Kikuchi, J.; Hasebe, N.; Kashiwagi, T.; Takashima, T.; Takahashi, K.; Nakano, T.; Nagaoka, S.;

Results From the First‐in‐Human Study With Ozanimod, a Novel, Selective Sphingosine‐1‐Phosphate Receptor Modulator

PubMed Central

Hartung, Jeffrey P.; Peach, Robert J.; Boehm, Marcus F.; Rosen, Hugh; Smith, Heather; Brooks, Jennifer L.; Timony, Gregg A.; Olson, Allan D.; Gujrathi, Sheila; Frohna, Paul A.

2017-01-01

Abstract The sphingosine‐1‐phosphate 1 receptor (S1P1R) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R receptors in clinical development for the treatment of chronic immune‐mediated, inflammatory diseases. This first‐in‐human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose‐escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose‐limiting toxicities. The most common ozanimod‐related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady‐state volume of distribution (73–101 L/kg), moderate oral clearance (204–227 L/h), and an elimination half‐life of approximately 17 to 21 hours. Ozanimod produced a robust dose‐dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose‐dependent negative chronotropic effect was observed following the first dose, with the dose‐escalation regimen attenuating the first‐dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once‐daily regimens under clinical investigation. PMID:28398597

The UF/NCI family of hybrid computational phantoms representing the current US population of male and female children, adolescents, and adults—application to CT dosimetry

NASA Astrophysics Data System (ADS)

Geyer, Amy M.; O'Reilly, Shannon; Lee, Choonsik; Long, Daniel J.; Bolch, Wesley E.

2014-09-01

Substantial increases in pediatric and adult obesity in the US have prompted a major revision to the current UF/NCI (University of Florida/National Cancer Institute) family of hybrid computational phantoms to more accurately reflect current trends in larger body morphometry. A decision was made to construct the new library in a gridded fashion by height/weight without further reference to age-dependent weight/height percentiles as these become quickly outdated. At each height/weight combination, circumferential parameters were defined and used for phantom construction. All morphometric data for the new library were taken from the CDC NHANES survey data over the time period 1999-2006, the most recent reported survey period. A subset of the phantom library was then used in a CT organ dose sensitivity study to examine the degree to which body morphometry influences the magnitude of organ doses for patients that are underweight to morbidly obese in body size. Using primary and secondary morphometric parameters, grids containing 100 adult male height/weight bins, 93 adult female height/weight bins, 85 pediatric male height/weight bins and 73 pediatric female height/weight bins were constructed. These grids served as the blueprints for construction of a comprehensive library of patient-dependent phantoms containing 351 computational phantoms. At a given phantom standing height, normalized CT organ doses were shown to linearly decrease with increasing phantom BMI for pediatric males, while curvilinear decreases in organ dose were shown with increasing phantom BMI for adult females. These results suggest that one very useful application of the phantom library would be the construction of a pre-computed dose library for CT imaging as needed for patient dose-tracking.

Radiation-quality dependent cellular response in mutation induction in normal human cells.

PubMed

Suzuki, Masao; Tsuruoka, Chizuru; Uchihori, Yukio; Kitamura, Hisashi; Liu, Cui Hua

2009-09-01

We studied cellular responses in normal human fibroblasts induced with low-dose (rate) or low-fluence irradiations of different radiation types, such as gamma rays, neutrons and high linear energy transfer (LET) heavy ions. The cells were pretreated with low-dose (rate) or low-fluence irradiations (approximately 1 mGy/7-8 h) of 137Cs gamma rays, 241Am-Be neutrons, helium, carbon and iron ions before irradiations with an X-ray challenging dose (1.5 Gy). Helium (LET = 2.3 keV/microm), carbon (LET = 13.3 keV/microm) and iron (LET = 200 keV/microm) ions were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No difference in cell-killing effect, measured by a colony forming assay, was observed among the pretreatment with different radiation types. In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. In the case of the pretreatment of heavy ions, X-ray-induced mutation was around 1.8 times higher in helium-ion pretreated and 4.0 times higher in carbon-ion pretreated cells than in unpretreated cells (X-ray challenging dose alone). However, the mutation frequency in cells pretreated with iron ions was the same level as either unpretreated or gamma-ray pretreated cells. In contrast, it was reduced at 0.15 times in cells pretreated with neutrons when compared to unpretreated cells. The results show that cellular responses caused by the influence of hprt mutation induced in cells pretreated with low-dose-rate or low-fluence irradiations of different radiation types were radiation-quality dependent manner.

Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome.

PubMed

Casero, David; Gill, Kirandeep; Sridharan, Vijayalakshmi; Koturbash, Igor; Nelson, Gregory; Hauer-Jensen, Martin; Boerma, Marjan; Braun, Jonathan; Cheema, Amrita K

2017-08-18

Space travel is associated with continuous low dose rate exposure to high linear energy transfer (LET) radiation. Pathophysiological manifestations after low dose radiation exposure are strongly influenced by non-cytocidal radiation effects, including changes in the microbiome and host gene expression. Although the importance of the gut microbiome in the maintenance of human health is well established, little is known about the role of radiation in altering the microbiome during deep-space travel. Using a mouse model for exposure to high LET radiation, we observed substantial changes in the composition and functional potential of the gut microbiome. These were accompanied by changes in the abundance of multiple metabolites, which were related to the enzymatic activity of the predicted metagenome by means of metabolic network modeling. There was a complex dynamic in microbial and metabolic composition at different radiation doses, suggestive of transient, dose-dependent interactions between microbial ecology and signals from the host's cellular damage repair processes. The observed radiation-induced changes in microbiota diversity and composition were analyzed at the functional level. A constitutive change in activity was found for several pathways dominated by microbiome-specific enzymatic reactions like carbohydrate digestion and absorption and lipopolysaccharide biosynthesis, while the activity in other radiation-responsive pathways like phosphatidylinositol signaling could be linked to dose-dependent changes in the abundance of specific taxa. The implication of microbiome-mediated pathophysiology after low dose ionizing radiation may be an unappreciated biologic hazard of space travel and deserves experimental validation. This study provides a conceptual and analytical basis of further investigations to increase our understanding of the chronic effects of space radiation on human health, and points to potential new targets for intervention in adverse radiation effects.

Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Burton, Page; Mechoulam, Raphael

2004-01-01

Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.

Tumor induction in mice after local irradiation with single doses of either carbon-ion beams or gamma rays.

PubMed

Ando, Koichi; Koike, Sachiko; Ohmachi, Yasushi; Ando, Yutaka; Kobashi, Gen

2014-12-01

To determine the dose-dependent relative biological effectiveness (RBE) for tumor prevalence in mice receiving single localized doses to their right leg of either carbon ions (15, 45 or 75 keV/μm) or 137Cs gamma rays. A total of 1647 female C3H mice were irradiated to their hind legs with a localized dose of either reference gamma rays or 15, 45 or 75 keV/μm carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during their three-year life span, and the dimensions of any tumors found were measured with a caliper. The tumor induction frequency was calculated by Kaplan-Meier analysis. The incidence of tumors from 50 Gy of 45 keV/μm carbon ions was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15 keV/μm carbon ions induced significantly fewer tumors than did gamma rays. RBE values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were calculated for 15, 45 or 75 keV/μm carbon-ion beams, respectively. Fibrosarcoma predominated, with no Linear Energy Transfer (LET)-dependent differences in the tumor histology. Experiments measuring the late effect of leg skin shrinkage suggested that the carcinogenic damage of 15 keV/μm carbon ions would be less than that of gamma rays. We conclude that patients receiving radiation doses to their normal tissues would face less risk of secondary tumor induction by carbon ions of intermediate LET values compared to equivalent doses of photons.

Single- and double-strand break formation in DNA irradiated in aqueous solution: dependence on dose and OH radical scavenger concentration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siddiqi, M.A.; Bothe, E.

The yields of single- and double-strand breaks (SSB and DSB) in calf thymus DNA, after /sup 60/Co gamma irradiation in dilute aqueous solution, have been determined via molecular weight measurements using a low-angle laser light scattering technique. The irradiations were administered to N/sub 2/O-containing solutions of DNA in the absence and presence of oxygen and with different concentrations of the OH radical scavengers phenol, tertiary butanol, and methanol. OH radicals were found to produce SSB linearly with dose with a G value of 55 nmol J-1 and 54 nmol J-1 in deoxygenated and oxygenated solutions, respectively. DSB were formed accordingmore » to a linear-quadratic dose relationship and the G value of linearly formed DSB were GDSB alpha(r.t.) = 3.5 nmol J-1 in deoxygenated and 3.2 nmol J-1 in oxygenated solution. The ratio of GSSB/GDSB alpha(r.t.) = gamma of 19 +/- 6 was independent of the scavenger concentration in the case of tertiary butanol and methanol-containing solutions. GDSB alpha(r.t.) is interpreted to result from a radical site transferred from a sugar moiety of the cleaved strand to the complementary intact strand. This process of radical transfer and subsequent cleavage of the second strand occurs with a probability of about 6 +/- 2% in the presence of oxygen at all scavenger concentrations studied. These data on scavenging capacity on GDSB alpha(r.t.) suggest that the double-strand breakage produced via radical transfer remains higher than that resulting from direct effect, up to scavenging capacities of about 10(9) s-1.« less

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PubMed

Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

2009-01-01

In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Evaluation of the dosimetric properties of a diode detector for small field proton radiosurgery

PubMed Central

Teran, Anthony V.; Slater, Jerry D.; Slater, James M.; Wroe, Andrew J.

2015-01-01

The small fields and sharp gradients typically encountered in proton radiosurgery require high spatial resolution dosimetric measurements, especially below 1–2 cm diameters. Radiochromic film provides high resolution, but requires postprocessing and special handling. Promising alternatives are diode detectors with small sensitive volumes (SV) that are capable of high resolution and real‐time dose acquisition. In this study we evaluated the PTW PR60020 proton dosimetry diode using radiation fields and beam energies relevant to radiosurgery applications. Energies of 127 and 157 MeV (9.7 to 15 cm range) and initial diameters of 8, 10, 12, and 20 mm were delivered using single‐stage scattering and four modulations (0, 15, 30, and 60 mm) to a water tank in our treatment room. Depth dose and beam profile data were compared with PTW Markus N23343 ionization chamber, EBT2 Gafchromic film, and Monte Carlo simulations. Transverse dose profiles were measured using the diode in "edge‐on" orientation or EBT2 film. Diode response was linear with respect to dose, uniform with dose rate, and showed an orientation‐dependent (i.e., beam parallel to, or perpendicular to, detector axis) response of less than 1%. Diode vs. Markus depth‐dose profiles, as well as Markus relative dose ratio vs. simulated dose‐weighted average lineal energy plots, suggest that any LET‐dependent diode response is negligible from particle entrance up to the very distal portion of the SOBP for the energies tested. Finally, while not possible with the ionization chamber due to partial volume effects, accurate diode depth‐dose measurements of 8, 10, and 12 mm diameter beams were obtained compared to Monte Carlo simulations. Because of the small SV that allows measurements without partial volume effects and the capability of submillimeter resolution (in edge‐on orientation) that is crucial for small fields and high‐dose gradients (e.g., penumbra, distal edge), as well as negligible LET dependence over nearly the full the SOBP, the PTW proton diode proved to be a useful high‐resolution, real‐time metrology device for small proton field radiation measurements such as would be encountered in radiosurgery applications. PACS numbers: 87.56.‐v, 87.56.jf, 87.56.Fc PMID:26699554

Biological impact of low dose-rate simulated solar particle event radiation in vivo.

PubMed

Chang, P Y; Doppalapudi, R; Bakke, J; Wang, A; Menda, S; Davis, Z

2010-08-01

C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure.

Radiation-induced genomic instability: radiation quality and dose response

NASA Technical Reports Server (NTRS)

Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.

2003-01-01

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Feasibility of a semiconductor dosimeter to monitor skin dose in interventional radiology.

PubMed

Meyer, P; Regal, R; Jung, M; Siffert, P; Mertz, L; Constantinesco, A

2001-10-01

The design and preliminary test results of a semiconductor silicon dosimeter are presented in this article. Use of this dosimeter is foreseen for real-time skin dose control in interventional radiology. The strong energy dependence of this kind of radiation detector is well overcome by filtering the silicon diode. Here, the optimal filter features have been calculated by numerical Monte Carlo simulations. A prototype has been built and tested in a radiological facility. The first experimental results show a good match between the filtered semiconductor diode response and an ionization chamber response, within 2% fluctuation in a 2.2 to 4.1 mm Al half-value layer (HVL) energy range. Moreover, the semiconductor sensor response is linear from 0.02 Gy/min to at least 6.5 Gy/min, covering the whole dose rate range found in interventional radiology. The results show that a semiconductor dosimeter could be used to monitor skin dose during the majority of procedures using x-rays below 150 keV. The use of this device may assist in avoiding radiation-induced skin injuries and lower radiation levels during interventional procedures.

Multichannel dosemeter and Al2O3:C optically stimulated luminescence fibre sensors for use in radiation therapy: evaluation with electron beams.

PubMed

Magne, S; Auger, L; Bordy, J M; de Carlan, L; Isambert, A; Bridier, A; Ferdinand, P; Barthe, J

2008-01-01

This article proposes an innovative multichannel optically stimulated luminescence (OSL) dosemeter for on-line in vivo dose verification in radiation therapy. OSL fibre sensors incorporating small Al(2)O(3):C fibre crystals (TLD(500)) have been tested with an X-ray generator. A reproducible readout procedure should reduce the fading-induced uncertainty ( approximately - 1% per decade). OSL readouts are temperature-dependent [ approximately 0.3% K(-1) when OSL stimulation is performed at the same temperature as irradiation; approximately 0.16% K(-1) after thermalisation (20 degrees C)]. Sensor calibration and depth-dose measurements with electron beams have been performed with a Saturne 43 linear accelerator in reference conditions at CEA-LNHB (ionising radiation reference laboratory in France). Predosed OSL sensors show a good repeatability in multichannel operation and independence versus electron energy in the range (9, 18 MeV). The difference between absorbed doses measured by OSL and an ionisation chamber were within +/-0.9% (for a dose of about 1 Gy) despite a sublinear calibration curve.

Topical Review: Polymer gel dosimetry

PubMed Central

Baldock, C; De Deene, Y; Doran, S; Ibbott, G; Jirasek, A; Lepage, M; McAuley, K B; Oldham, M; Schreiner, L J

2010-01-01

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented. PMID:20150687

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

PubMed

Abend, M; Pfeiffer, R M; Ruf, C; Hatch, M; Bogdanova, T I; Tronko, M D; Hartmann, J; Meineke, V; Mabuchi, K; Brenner, A V

2013-10-15

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

SIMPLIFIED PRACTICAL TEST METHOD FOR PORTABLE DOSE METERS USING SEVERAL SEALED RADIOACTIVE SOURCES.

PubMed

Mikamoto, Takahiro; Yamada, Takahiro; Kurosawa, Tadahiro

2016-09-01

Sealed radioactive sources which have small activity were employed for the determination of response and tests for non-linearity and energy dependence of detector responses. Close source-to-detector geometry (at 0.3 m or less) was employed to practical tests for portable dose meters to accumulate statistically sufficient ionizing currents. Difference between response in the present experimentally studied field and in the reference field complied with ISO 4037 due to non-uniformity of radiation fluence at close geometry was corrected by use of Monte Carlo simulation. As a consequence, corrected results were consistent with the results obtained in the ISO 4037 reference field within their uncertainties. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of Al2O3:C optically stimulated luminescence (OSL) dosimeters for passive dosimetry of high-energy photon and electron beams in radiotherapy.

PubMed

Yukihara, E G; Mardirossian, G; Mirzasadeghi, M; Guduru, S; Ahmad, S

2008-01-01

This article investigates the performance of Al2O3: C optically stimulated luminescence dosimeters (OSLDs) for application in radiotherapy. Central-axis depth dose curves and optically stimulated luminescence (OSL) responses were obtained in a water phantom for 6 and 18 MV photons, and for 6, 9, 12, 16, and 20 MeV electron beams from a Varian 21EX linear accelerator. Single OSL measurements could be repeated with a precision of 0.7% (one standard deviation) and the differences between absorbed doses measured with OSLDs and an ionization chamber were within +/- 1% for photon beams. Similar results were obtained for electron beams in the low-gradient region after correction for a 1.9% photon-to-electron bias. The distance-to-agreement values were of the order of 0.5-1.0 mm for electrons in high dose gradient regions. Additional investigations also demonstrated that the OSL response dependence on dose rate, field size, and irradiation temperature is less than 1% in the conditions of the present study. Regarding the beam energy/quality dependence, the relative response of the OSLD for 18 MV was (0.51 +/- 0.48)% of the response for the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam was in average 1.9% higher, but this result requires further confirmation. The relative response did not seem to vary with electron energy at dmax within the experimental uncertainties (0.5% in average) and, therefore, a fixed correction factor of 1.9% eliminated the energy dependence in our experimental conditions.

Evaluation of Al{sub 2}O{sub 3}:C optically stimulated luminescence (OSL) dosimeters for passive dosimetry of high-energy photon and electron beams in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yukihara, E. G.; Mardirossian, G.; Mirzasadeghi, M.

This article investigates the performance of Al{sub 2}O{sub 3}:C optically stimulated luminescence dosimeters (OSLDs) for application in radiotherapy. Central-axis depth dose curves and optically stimulated luminescence (OSL) responses were obtained in a water phantom for 6 and 18 MV photons, and for 6, 9, 12, 16, and 20 MeV electron beams from a Varian 21EX linear accelerator. Single OSL measurements could be repeated with a precision of 0.7% (one standard deviation) and the differences between absorbed doses measured with OSLDs and an ionization chamber were within {+-}1% for photon beams. Similar results were obtained for electron beams in the low-gradientmore » region after correction for a 1.9% photon-to-electron bias. The distance-to-agreement values were of the order of 0.5-1.0 mm for electrons in high dose gradient regions. Additional investigations also demonstrated that the OSL response dependence on dose rate, field size, and irradiation temperature is less than 1% in the conditions of the present study. Regarding the beam energy/quality dependence, the relative response of the OSLD for 18 MV was (0.51{+-}0.48)% of the response for the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam was in average 1.9% higher, but this result requires further confirmation. The relative response did not seem to vary with electron energy at d{sub max} within the experimental uncertainties (0.5% in average) and, therefore, a fixed correction factor of 1.9% eliminated the energy dependence in our experimental conditions.« less

Induction and quantification of gammma-H2AX foci following cx- and gamma-irradiaton

NASA Technical Reports Server (NTRS)

Leatherbarrow, E. L.; Cucinotta, F. A.; O'Neill, Peter

2004-01-01

Following DNA damage the histone H2AX becomes phosphorylated and can be visualised by immunofluorescence as an indicator of DSBs in individual cells. Using a wild type hamster cell line (V79-4) exposed to either a-particles or to Co-60 gamma-rays to induce DNA DSBs at different doses (20-200OmGy), the dose dependent induction of gamma-H2AX foci were scored both manually (by eye) and using image analysis. A linearly dependence on dose was found for both radiations. The number of DSBs determined by image analysis after a post-irradiation period of 30 minutes at 37 C, is 16.6 foci/cell/Gy for alpha-irradiation and 12.2 foci/cell/Gy for gamma-irradiation; the latter being 3-4 times the levels observed by eye and comparable to gamma-radiation-induced levels of prompt DSBs more recently reported using pulse field gel electrophoresis (approx. 16 DSBs/Gy). The average size of the gamma-H2AX foci induced by alpha-irradiation (0.30 square micrometers) is approximately 1.5 times larger than those induced by gamma-irradiation (0.19 square micrometers). The timescale of induction and removal of DSBs up to 24 hours post-irradiation, was investigated with gamma-H2AX foci levels found to remain significantly higher than controls for 4 or 6 hours in gamma-irradiated samples or alpha irradiated samples, respectively. These results demonstrate that not only gamma radiation but also alpha-radiation induce phosphorylation of the H2AX histone in response to DSBs even at low doses (20mGy for gamma-rays, 1 track/cell on average for alpha-particles) and the variation in size and dephosphorylation of the induced foci is dependent on radiation quality (LET).

Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus.

PubMed

Hada, Megumi; Chappell, Lori J; Wang, Minli; George, Kerry A; Cucinotta, Francis A

2014-10-01

The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/μm), silicon (99 keV/μm) or Fe (175 keV/μm), Fe (195 keV/μm) or Fe (240 keV/μm) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses.

LAURISTON S. TAYLOR LECTURE ON RADIATION PROTECTION AND MEASURMENTS: WHAT MAKES PARTICLE RADIATION SO EFFECTIVE?

PubMed Central

Blakely, Eleanor A.

2012-01-01

The scientific basis for the physical and biological effectiveness of particle radiations has emerged from many decades of meticulous basic research. A diverse array of biologically relevant consequences at the molecular, cellular, tissue, and organism level have been reported, but what are the key processes and mechanisms that make particle radiation so effective, and what competing processes define dose dependences? Recent studies have shown that individual genotypes control radiation-regulated genes and pathways in response to radiations of varying ionization density. The fact that densely ionizing radiations can affect different gene families than sparsely ionizing radiations, and that the effects are dose- and time-dependent has opened up new areas of future research. The complex microenvironment of the stroma, and the significant contributions of the immune response have added to our understanding of tissue-specific differences across the linear energy transfer (LET) spectrum. The importance of targeted vs. nontargeted effects remain a thorny, but elusive and important contributor to chronic low dose radiation effects of variable LET that still needs further research. The induction of cancer is also LET-dependent, suggesting different mechanisms of action across the gradient of ionization density. The focus of this 35th Lauriston S. Taylor Lecture is to chronicle the step-by-step acquisition of experimental clues that have refined our understanding of what makes particle radiation so effective, with emphasis on the example of radiation effects on the crystalline lens of the human eye. PMID:23032880

Validity of linear measurements of the jaws using ultralow-dose MDCT and the iterative techniques of ASIR and MBIR.

PubMed

Al-Ekrish, Asma'a A; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Widmann, Gerlig

2016-10-01

To assess the comparability of linear measurements of dental implant sites recorded from multidetector computed tomography (MDCT) images obtained using standard-dose filtered backprojection (FBP) technique with those from various ultralow doses combined with FBP, adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR) techniques. The results of the study may contribute to MDCT dose optimization for dental implant site imaging. MDCT scans of two cadavers were acquired using a standard reference protocol and four ultralow-dose test protocols (TP). The volume CT dose index of the different dose protocols ranged from a maximum of 30.48-36.71 mGy to a minimum of 0.44-0.53 mGy. All scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Linear measurements were recorded from standardized images of the jaws by two examiners. Intra- and inter-examiner reliability of the measurements were analyzed using Cronbach's alpha and inter-item correlation. Agreement between the measurements obtained with the reference-dose/FBP protocol and each of the test protocols was determined with Bland-Altman plots and linear regression. Statistical significance was set at a P-value of 0.05. No systematic variation was found between the linear measurements obtained with the reference protocol and the other imaging protocols. The only exceptions were TP3/ASIR-50 (bone kernel) and TP4/ASIR-100 (bone and standard kernels). The mean measurement differences between these three protocols and the reference protocol were within ±0.1 mm, with the 95 % confidence interval limits being within the range of ±1.15 mm. A nearly 97.5 % reduction in dose did not significantly affect the height and width measurements of edentulous jaws regardless of the reconstruction algorithm used.

Dosimetric characterization with 62 MeV protons of a silicon-segmented detector for 2D dose verifications in radiotherapy

NASA Astrophysics Data System (ADS)

Talamonti, C.; Bucciolini, M.; Marrazzo, L.; Menichelli, D.; Bruzzi, M.; Cirrone, G. A. P.; Cuttone, G.; LoJacono, P.

2008-10-01

Due to the features of the modern radiotherapy techniques, namely intensity modulated radiation therapy and proton therapy, where high spatial dose gradients are often present, detectors to be employed for 2D dose verifications have to satisfy very narrow requirements. In particular they have to show high spatial resolution. In the framework of the European Integrated Project—Methods and Advanced Equipment for Simulation and Treatment in Radio-Oncology (MAESTRO, no. LSHC-CT-2004-503564), a dosimetric detector adequate for 2D pre-treatment dose verifications was developed. It is a modular detector, based on a monolithic silicon-segmented sensor, with an n-type implantation on an epitaxial p-type layer. Each pixel element is 2×2 mm 2 and the distance center-to-center is 3 mm. The sensor is composed of 21×21 pixels. In this paper, we report the dosimetric characterization of the system with a proton beam. The sensor was irradiated with 62 MeV protons for clinical treatments at INFN-Laboratori Nazionali del Sud (LNS) Catania. The studied parameters were repeatability of a same pixel, response linearity versus absorbed dose, and dose rate and dependence on field size. The obtained results are promising since the performances are within the project specifications.

Radiation-induced change of optical property of hydroxypropyl cellulose hydrogel containing methacrylate compounds: As a basis for development of a new type of radiation dosimeter

NASA Astrophysics Data System (ADS)

Yamashita, Shinichi; Hiroki, Akihiro; Taguchi, Mitsumasa

2014-08-01

Hydrogels with matrix of a cellulose derivative, hydrogel of hydroxpropyl cellulose (HPC), containing two of methacrylate compounds (2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) dimethacrylate (9G)) were irradiated with 60Co γ-rays. The gels become white with irradiation, and thus, could be candidates of a new type of radiation dosimeter utilized in radiation therapy because the gels become white with irradiation and can be confirmed directly by human eyes even at low doses of 1-2 Gy. Radiation-induced change of optical properties, haze value and UV-vis absorption spectrum, of the irradiated gels was measured. Dose response of the white turbidity appearance was different for different compositions of the methacrylate compounds as well as for different dose rates. The degree of the radiation-induced white turbidity was quantified by measuring haze value, showing linear dose response in low dose region (<2 Gy). We also analyzed the gels with a UV-vis spectrometer and HEMA- and 9G-rich gels gave different spectral shapes, indicating that there are at least two mechanisms leading to the white turbidity. In addition, dose rate dependence was smaller for 9G-rich gels than HEMA-rich gels in the range of 0.015-1.5 Gy/min.

A methodology to investigate the impact of image distortions on the radiation dose when using magnetic resonance images for planning

NASA Astrophysics Data System (ADS)

Yan, Yue; Yang, Jinzhong; Beddar, Sam; Ibbott, Geoffrey; Wen, Zhifei; Court, Laurence E.; Hwang, Ken-Pin; Kadbi, Mo; Krishnan, Sunil; Fuller, Clifton D.; Frank, Steven J.; Yang, James; Balter, Peter; Kudchadker, Rajat J.; Wang, Jihong

2018-04-01

We developed a novel technique to study the impact of geometric distortion of magnetic resonance imaging (MRI) on intensity-modulated radiation therapy treatment planning. The measured 3D datasets of residual geometric distortion (a 1.5 T MRI component of an MRI linear accelerator system) was fitted with a second-order polynomial model to map the spatial dependence of geometric distortions. Then the geometric distortion model was applied to computed tomography (CT) image and structure data to simulate the distortion of MRI data and structures. Fourteen CT-based treatment plans were selected from patients treated for gastrointestinal, genitourinary, thoracic, head and neck, or spinal tumors. Plans based on the distorted CT and structure data were generated (as the distorted plans). Dose deviations of the distorted plans were calculated and compared with the original plans to study the dosimetric impact of MRI distortion. The MRI geometric distortion led to notable dose deviations in five of the 14 patients, causing loss of target coverage of up to 3.68% and dose deviations to organs at risk in three patients, increasing the mean dose to the chest wall by up to 6.19 Gy in a gastrointestinal patient, and increases the maximum dose to the lung by 5.17 Gy in a thoracic patient.

GafChromic EBT film dosimetry with flatbed CCD scanner: a novel background correction method and full dose uncertainty analysis.

PubMed

Saur, Sigrun; Frengen, Jomar

2008-07-01

Film dosimetry using radiochromic EBT film in combination with a flatbed charge coupled device scanner is a useful method both for two-dimensional verification of intensity-modulated radiation treatment plans and for general quality assurance of treatment planning systems and linear accelerators. Unfortunately, the response over the scanner area is nonuniform, and when not corrected for, this results in a systematic error in the measured dose which is both dose and position dependent. In this study a novel method for background correction is presented. The method is based on the subtraction of a correction matrix, a matrix that is based on scans of films that are irradiated to nine dose levels in the range 0.08-2.93 Gy. Because the response of the film is dependent on the film's orientation with respect to the scanner, correction matrices for both landscape oriented and portrait oriented scans were made. In addition to the background correction method, a full dose uncertainty analysis of the film dosimetry procedure was performed. This analysis takes into account the fit uncertainty of the calibration curve, the variation in response for different film sheets, the nonuniformity after background correction, and the noise in the scanned films. The film analysis was performed for film pieces of size 16 x 16 cm, all with the same lot number, and all irradiations were done perpendicular onto the films. The results show that the 2-sigma dose uncertainty at 2 Gy is about 5% and 3.5% for landscape and portrait scans, respectively. The uncertainty gradually increases as the dose decreases, but at 1 Gy the 2-sigma dose uncertainty is still as good as 6% and 4% for landscape and portrait scans, respectively. The study shows that film dosimetry using GafChromic EBT film, an Epson Expression 1680 Professional scanner and a dedicated background correction technique gives precise and accurate results. For the purpose of dosimetric verification, the calculated dose distribution can be compared with the film-measured dose distribution using a dose constraint of 4% (relative to the measured dose) for doses between 1 and 3 Gy. At lower doses, the dose constraint must be relaxed.

MO-F-16A-02: Simulation of a Medical Linear Accelerator for Teaching Purposes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlone, M; Lamey, M; Anderson, R

Purpose: Detailed functioning of linear accelerator physics is well known. Less well developed is the basic understanding of how the adjustment of the linear accelerator's electrical components affects the resulting radiation beam. Other than the text by Karzmark, there is very little literature devoted to the practical understanding of linear accelerator functionality targeted at the radiotherapy clinic level. The purpose of this work is to describe a simulation environment for medical linear accelerators with the purpose of teaching linear accelerator physics. Methods: Varian type lineacs were simulated. Klystron saturation and peak output were modelled analytically. The energy gain of anmore » electron beam was modelled using load line expressions. The bending magnet was assumed to be a perfect solenoid whose pass through energy varied linearly with solenoid current. The dose rate calculated at depth in water was assumed to be a simple function of the target's beam current. The flattening filter was modelled as an attenuator with conical shape, and the time-averaged dose rate at a depth in water was determined by calculating kerma. Results: Fifteen analytical models were combined into a single model called SIMAC. Performance was verified systematically by adjusting typical linac control parameters. Increasing klystron pulse voltage increased dose rate to a peak, which then decreased as the beam energy was further increased due to the fixed pass through energy of the bending magnet. Increasing accelerator beam current leads to a higher dose per pulse. However, the energy of the electron beam decreases due to beam loading and so the dose rate eventually maximizes and the decreases as beam current was further increased. Conclusion: SIMAC can realistically simulate the functionality of a linear accelerator. It is expected to have value as a teaching tool for both medical physicists and linear accelerator service personnel.« less

Caffeine and length dependence of staircase potentiation in skeletal muscle.

PubMed

Rassier, D E; Tubman, L A; MacIntosh, B R

1998-01-01

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this results in an optimal length for twitch contractions that is longer than optimal length for tetanic contractions. Caffeine abolishes this length dependence of Ca2+ sensitivity. Muscle length (ML) also affects the degree of staircase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis that caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased length (DT = 1.47 - 0.05 ML, r2 = 0.95, where DT is developed tension). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship between staircase potentiation and muscle length was diminished at the lower caffeine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009 ML, r2 = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Caffeine also suppressed the length dependence of staircase potentiation, suggesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.

SU-E-QI-15: Single Point Dosimetry by Means of Cerenkov Radiation Energy Transfer (CRET)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volotskova, O; Jenkins, C; Xing, L

2014-06-15

Purpose: Cerenkov light is generated when a charged particles with energy greater then 250 keV, moves faster than the speed of light in a given medium. Both x-ray photons and electrons produce optical Cerenkov photons during the static megavoltage linear accelerator (LINAC) operational mode. Recently, Cerenkov radiation gained considerable interest as possible candidate as a new imaging modality. Optical signals generated by Cerenkov radiation may act as a surrogate for the absorbed superficial radiation dose. We demonstrated a novel single point dosimetry method for megavoltage photon and electron therapy utilizing down conversion of Cerenkov photons. Methods: The custom build signalmore » characterization system was used: a sample holder (probe) with adjacent light tight compartments was connected via fiber-optic cables to a photon counting photomultiplier tube (PMT). One compartment contains a medium only while the other contains medium and red-shifting nano-particles (Q-dots, nanoclusters). By taking the difference between the two signals (Cerenkov photons and CRET photons) we obtain a measure of the down-converted light, which we expect to be proportional to dose as measured with an adjacent ion chamber. Experimental results are compared to Monte Carlo simulations performed using the GEANT4 code. Results: The signal correlation between CR signal, CRET readings and dose produced by LINAC at a single point were investigated. The experimental results were compared with simulations. The dose linearity, signal to noise ratio and dose rate dependence were tested with custom build CRET based probe. Conclusion: Performance characteristics of the proposed single point CRET based probe were evaluated. The direct use of the induced Cerenkov emission and CRET in an irradiated single point volume as an indirect surrogate for the imparted dose was investigated. We conclude that CRET is a promising optical based dosimetry method that offers advantages over those already proposed.« less

Surface and buildup dose characteristics for 6, 10, and 18 MV photons from an Elekta Precise linear accelerator.

PubMed

Klein, Eric E; Esthappan, Jacqueline; Li, Zuofeng

2003-01-01

Understanding head scatter characteristics of photon beams is vital to properly commission treatment planning (TP) algorithms. Simultaneously, having definitive surface and buildup region dosimetry is important to optimize bolus. The Elekta Precise linacs have unique beam flattening filter configurations for each photon beam (6, 10, and 18 MV) in terms of material and location. We performed a comprehensive set of surface and buildup dose measurements with a thin window parallel-plate (PP) chamber to examine effects of field size (FS), source-to-skin distance (SSD), and attenuating media. Relative ionization data were converted to fractional depth dose (FDD) after correcting for bias effects and using the Gerbi method to account for chamber characteristics. Data were compared with a similar vintage Varian linac. At short SSDs the surface and buildup dose characteristics were similar to published data for Varian and Elekta accelerators. The FDD at surface (FDD(0)) for 6, 10, and 18 MV photons was 0.171, 0.159, and 0.199, respectively, for a 15x15 cm2, 100 cm SSD field. A blocking tray increased FDD(0) to 0.200, 0.200, and 0.256, while the universal wedge decreased FDD(0) to 0.107, 0.124, and 0.176. FDD(0) increased linearly with FS (approximately 1.16%/cm). FDD(0) decreased exponentially for 10 and 18 MV with increasing SSD. However, the 6 MV FDD(0) actually increased slightly with increasing SSD. This is likely due to the unique distal flattening filter for 6 MV. The measured buildup curves have been used to optimize TP calculations and guide bolus decisions. Overall the FDD(0) and buildup doses were very similar to published data. Of interest were the relatively low 10 MV surface doses, and the 6 MV FDD(0)'s dependence on SSD.

Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies.

PubMed

Balásházy, Imre; Farkas, Arpád; Madas, Balázs Gergely; Hofmann, Werner

2009-06-01

Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. The results obtained suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high, even at low average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10-100 mGy.

Implementation of dual-energy technique for virtual monochromatic and linearly mixed CBCTs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Hao; Giles, William; Ren Lei

Purpose: To implement dual-energy imaging technique for virtual monochromatic (VM) and linearly mixed (LM) cone beam CTs (CBCTs) and to demonstrate their potential applications in metal artifact reduction and contrast enhancement in image-guided radiation therapy (IGRT). Methods: A bench-top CBCT system was used to acquire 80 kVp and 150 kVp projections, with an additional 0.8 mm tin filtration. To implement the VM technique, these projections were first decomposed into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of VM CBCT on the metal artifact reduction was evaluated withmore » an in-house titanium-BB phantom. The optimal VM energy to maximize contrast-to-noise ratio (CNR) for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The LM technique was implemented by linearly combining the low-energy (80 kVp) and high-energy (150 kVp) CBCTs. The dose partitioning between low-energy and high-energy CBCTs was varied (20%, 40%, 60%, and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125, and 150 kVp. Results: The VM technique showed substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared to a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference of average noise levels measured in the phantom background was 1.2% between dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning are better than those of 150 kVp single-energy CBCTs. The average CNR for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low-contrast objects improved as dose partitioning was more heavily weighted toward low-energy (80 kVp) for LM CBCTs. Conclusions: Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared to single-energy CBCT acquired with equivalent dose.« less

Recombination in liquid-filled ionization chambers beyond the Boag limit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brualla-González, L.; Roselló, J.

Purpose: The high mass density and low mobilities of charge carriers can cause important recombination in liquid-filled ionization chambers (LICs). Saturation correction methods have been proposed for LICs. Correction methods for pulsed irradiation are based on Boag equation. However, Boag equation assumes that the charge ionized by one pulse is fully collected before the arrival of the next pulse. This condition does not hold in many clinical beams where the pulse repetition period may be shorter than the charge collection time, causing overlapping between charge carriers ionized by different pulses, and Boag equation is not applicable there. In this work,more » the authors present an experimental and numerical characterization of collection efficiencies in LICs beyond the Boag limit, with overlapping between charge carriers ionized by different pulses. Methods: The authors have studied recombination in a LIC array for different dose-per-pulse, pulse repetition frequency, and polarization voltage values. Measurements were performed in a Truebeam Linac using FF and FFF modalities. Dose-per-pulse and pulse repetition frequency have been obtained by monitoring the target current with an oscilloscope. Experimental collection efficiencies have been obtained by using a combination of the two-dose-rate method and ratios to the readout of a reference chamber (CC13, IBA). The authors have also used numerical simulation to complement the experimental data. Results: The authors have found that overlap significantly increases recombination in LICs, as expected. However, the functional dependence of collection efficiencies on the dose-per-pulse does not change (a linear dependence has been observed in the near-saturation region for different degrees of overlapping, the same dependence observed in the nonoverlapping scenario). On the other hand, the dependence of collection efficiencies on the polarization voltage changes in the overlapping scenario and does not follow that of Boag equation, the reason being that changing the polarization voltage also affects the charge collection time, thus changing the amount of overlapping. Conclusions: These results have important consequences for saturation correction methods for LICs. On one hand, the two-dose-rate method, which relies on the functional dependence of the collection efficiencies on dose-per-pulse, can also be used in the overlapping situation, provided that the two measurements needed to feed the method are performed at the same pulse repetition frequency (monitor unit rate). This result opens the door to computing collection efficiencies in LICs in many clinical setups where charge overlap in the LIC exists. On the other hand, correction methods based on the voltage-dependence of Boag equation like the three-voltage method or the modified two-voltage method will not work in the overlapping scenario due to the different functional dependence of collection efficiencies on the polarization voltage.« less

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects.

PubMed

Li, Zhaoyang; Hard, Marjie L; Andersen, Grit; Pabst, Günther; Wagener, Gilbert; Singh, Tejdip; Chin, Wai; Culm-Merdek, Kerry; Boltje, Ingrid; von Moltke, Lisa L

2014-04-01

To characterize the safety, tolerability, pharmacokinetics (PK) and dose proportionality of mipomersen after single subcutaneous (SC) administration to Japanese healthy subjects; and to compare the PK profiles of Japanese and Western subjects. 20 healthy first-generation Japanese male subjects were enrolled into one of three treatment cohorts (50, 100 and 200 mg SC) in a dose-escalation design. Within each cohort, subjects were randomized in a 4 : 1 ratio to receive mipomersen or placebo. Mipomersen was absorbed rapidly after SC administration; median tmax varied between 2 and 3 hours. After reaching peak levels, plasma concentrations of mipomersen decayed multiphasically with an initial distribution t1/2 in several hours and a terminal t1/2 of 261 - 393 hours. Mean Cmax increased in a dose-linear manner while all mean AUC from time 0 to different cut points increased slightly more than dose proportionally. Although mean terminal t1/2 varied in the dose range tested, it did not show dose-dependence. The PK profiles of mipomersen in Japanese subjects are similar to those observed in Western subjects. A single SC dose of 50 mg, 100 mg and 200 mg mipomersen was well tolerated by male Japanese subjects. Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects. Comparison of PK between Japanese and Western subjects does not support any need for dose adjustment in Japanese population in future clinical development.

Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

DOE PAGES

Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

2016-06-22

Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

SU-E-T-644: Evaluation of Angular Dependence Correction for 2D Array Detector Using for Quality Assurance of Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karthikeyan, N; Ganesh, K M; Vikraman, S

2014-06-15

Purpose: To evaluate the angular dependence correction for Matrix Evolution 2D array detector in quality assurance of volumetric modulated arc therapy(VMAT). Methods: Total ten patients comprising of different sites were planned for VMAT and taken for the study. Each plan was exposed on Matrix Evolution 2D array detector with Omnipro IMRT software based on the following three different methods using 6MV photon beams from Elekta Synergy linear accelerator. First method, VMAT plan was delivered on Matrix Evolution detector as it gantry mounted with dedicated holder with build-up of 2.3cm. Second, the VMAT plan was delivered with the static gantry anglemore » on to the table mounted setup. Third, the VMAT plan was delivered with actual gantry angle on Matrix Evolution detector fixed in Multicube phantom with gantry angle sensor and angular dependence correction were applied to quantify the plan quality. For all these methods, the corresponding QA plans were generated in TPS and the dose verification was done for both point and 2D fluence analysis with pass criteria of 3% dose difference and 3mm distance to agreement. Results: The measured point dose variation for the first method was observed as 1.58±0.6% of mean and SD with TPS calculated. For second and third method, the mean and standard deviation(SD) was observed as 1.67±0.7% and 1.85±0.8% respectively. The 2D fluence analysis of measured and TPS calculated has the mean and SD of 97.9±1.1%, 97.88±1.2% and 97.55±1.3% for first, second and third methods respectively. The calculated two-tailed Pvalue for point dose and 2D fluence analysis shows the insignificance with values of 0.9316 and 0.9015 respectively, among the different methods of QA. Conclusion: The qualitative evaluation of angular dependence correction for Matrix Evolution 2D array detector shows its competency in accuracy of quality assurance measurement of composite dose distribution of volumetric modulated arc therapy.« less

A REVIEW ON THE RADIATION THERAPY TECHNOLOGIST RECEIVED DOSE FROM INDUCED ACTIVATION IN HIGH-ENERGY MEDICAL LINEAR ACCELERATORS.

PubMed

Nourmohammadi, Bahareh; Mesbahi, Asghar

2018-06-01

Despite all advantages for using high-energy photons for radiotherapy, high-energy photon beams (≥10 MV) induce photonuclear and neutron capture interactions, which result in producing radionuclide byproducts inside the Linac head and bunker, exposing radiation therapy technologists (RTTs) and patients to excessive dose. By the use of higher photon energy, greater number of monitor unit, greater field size and adding treatment accessories, induced dose rate become greater in the isocenter mainly due to activation of high-Z materials inside the Linac head. Activated radionuclides disintegrate with γ, β+ and β- rays with half-lives between 2 min up to more than 5 years. Several researches estimated additional exposure to an RTT depend on treatment strategies, beam energy, and delay time before entrance to the treatment room between 0.1 and 4.9 mSv/y and proposed at least 2 min delay before entrance to the treatment room after treatments with high-energy photon beams.

Development of a flexible γ-ray detector using a liquid scintillation light guide (LSLG).

PubMed

Nomura, Kiyoshi; Yunoki, Akira; Hara, Masayuki; Morito, Yuko; Fujishima, Akira

2018-04-10

A flexible γ detector using a liquid scintillation light guide (LSLG) was developed. The analyzed pulse height (PHA) spectrum depended on the diameter, length and scintillator concentration of the LSLG, and the distance of a γ ray irradiation point from the head of photomultiplier tube (PMT). From the analysis of PHA spectrum, it was found that the count ratio of two divided channel regions linearly decreases as the distance from the PMT head increases. It was further found that the radiation dose rate can be estimated by setting the flexible LSLG tube to a circular shape since the count rate is proportional to the dose rate measured by a conventional NaI (Tl) scintillation detector. Therefore, a flexible and long LSLG detector using a single PMT is useful for determination of the dose rate and has a potential to detect local contaminations in a certain narrow space. Copyright © 2018. Published by Elsevier Ltd.

Application of the optically stimulated luminescence (OSL) technique for mouse dosimetry in micro-CT imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrigneaud, Jean-Marc; Courteau, Alan; Oudot, Alexandra

2013-12-15

Purpose: Micro-CT is considered to be a powerful tool to investigate various models of disease on anesthetized animals. In longitudinal studies, the radiation dose delivered by the micro-CT to the same animal is a major concern as it could potentially induce spurious effects in experimental results. Optically stimulated luminescence dosimeters (OSLDs) are a relatively new kind of detector used in radiation dosimetry for medical applications. The aim of this work was to assess the dose delivered by the CT component of a micro-SPECT (single-photon emission computed tomography)/CT camera during a typical whole-body mouse study, using commercially available OSLDs based onmore » Al{sub 2}O{sub 3}:C crystals.Methods: CTDI (computed tomography dose index) was measured in micro-CT with a properly calibrated pencil ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity in the range of doses delivered by the micro-CT. Dose measurements obtained with OSLDs were compared to those of the ionization chamber to correct for the radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were then investigated in phantoms and cadavers. A 30 mm diameter phantom, specifically designed to insert OSLDs, was used to assess radiation dose over a typical whole-body mouse imaging study. Eighteen healthy female BALB/c mice weighing 27.1 ± 0.8 g (1 SD) were euthanized for small animal measurements. OLSDs were placed externally or implanted internally in nine different locations by an experienced animal technician. Five commonly used micro-CT protocols were investigated.Results: CTDI measurements were between 78.0 ± 2.1 and 110.7 ± 3.0 mGy for the rat-like phantom and between 169.3 ± 4.6 and 203.6 ± 5.5 mGy for the mouse-like phantom. On average, the displayed CTDI at the operator console was underestimated by 1.19 for the rat-like phantom and 2.36 for the mouse-like phantom. OSLDs exhibited a reproducibility of 2.4% and good linearity was found between 60 and 450 mGy. The energy scaling factor was calculated to be between 1.80 ± 0.16 and 1.86 ± 0.16, depending on protocol used. In phantoms, mean doses to tissue over a whole-body CT examination were ranging from 186.4 ± 7.6 to 234.9 ± 7.1 mGy. In mice, mean doses to tissue in the mouse trunk (thorax, abdomen, pelvis, and flanks) were between 213.0 ± 17.0 and 251.2 ± 13.4 mGy. Skin doses (3 OSLDs) were much higher with average doses between 350.6 ± 25.3 and 432.5 ± 34.1 mGy. The dose delivered during a topogram was found to be below 10 mGy. Use of the multimouse bed of the system gave a significantly 20%–40% lower dose per animal (p < 0.05).Conclusions: Absorbed doses in micro-CT were found to be relatively high. In micro-SPECT/CT imaging, the micro-CT unit is mainly used to produce a localization frame. As a result, users should pay attention to adjustable CT parameters so as to minimize the radiation dose and avoid any adverse radiation effects which may interfere with biological parameters studied.« less

Application of the optically stimulated luminescence (OSL) technique for mouse dosimetry in micro-CT imaging.

PubMed

Vrigneaud, Jean-Marc; Courteau, Alan; Ranouil, Julien; Morgand, Loïc; Raguin, Olivier; Walker, Paul; Oudot, Alexandra; Collin, Bertrand; Brunotte, François

2013-12-01

Micro-CT is considered to be a powerful tool to investigate various models of disease on anesthetized animals. In longitudinal studies, the radiation dose delivered by the micro-CT to the same animal is a major concern as it could potentially induce spurious effects in experimental results. Optically stimulated luminescence dosimeters (OSLDs) are a relatively new kind of detector used in radiation dosimetry for medical applications. The aim of this work was to assess the dose delivered by the CT component of a micro-SPECT (single-photon emission computed tomography)∕CT camera during a typical whole-body mouse study, using commercially available OSLDs based on Al2O3:C crystals. CTDI (computed tomography dose index) was measured in micro-CT with a properly calibrated pencil ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity in the range of doses delivered by the micro-CT. Dose measurements obtained with OSLDs were compared to those of the ionization chamber to correct for the radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were then investigated in phantoms and cadavers. A 30 mm diameter phantom, specifically designed to insert OSLDs, was used to assess radiation dose over a typical whole-body mouse imaging study. Eighteen healthy female BALB∕c mice weighing 27.1 ± 0.8 g (1 SD) were euthanized for small animal measurements. OLSDs were placed externally or implanted internally in nine different locations by an experienced animal technician. Five commonly used micro-CT protocols were investigated. CTDI measurements were between 78.0 ± 2.1 and 110.7 ± 3.0 mGy for the rat-like phantom and between 169.3 ± 4.6 and 203.6 ± 5.5 mGy for the mouse-like phantom. On average, the displayed CTDI at the operator console was underestimated by 1.19 for the rat-like phantom and 2.36 for the mouse-like phantom. OSLDs exhibited a reproducibility of 2.4% and good linearity was found between 60 and 450 mGy. The energy scaling factor was calculated to be between 1.80 ± 0.16 and 1.86 ± 0.16, depending on protocol used. In phantoms, mean doses to tissue over a whole-body CT examination were ranging from 186.4 ± 7.6 to 234.9 ± 7.1 mGy. In mice, mean doses to tissue in the mouse trunk (thorax, abdomen, pelvis, and flanks) were between 213.0 ± 17.0 and 251.2 ± 13.4 mGy. Skin doses (3 OSLDs) were much higher with average doses between 350.6 ± 25.3 and 432.5 ± 34.1 mGy. The dose delivered during a topogram was found to be below 10 mGy. Use of the multimouse bed of the system gave a significantly 20%-40% lower dose per animal (p < 0.05). Absorbed doses in micro-CT were found to be relatively high. In micro-SPECT∕CT imaging, the micro-CT unit is mainly used to produce a localization frame. As a result, users should pay attention to adjustable CT parameters so as to minimize the radiation dose and avoid any adverse radiation effects which may interfere with biological parameters studied.

Linearity and reproducibility response of Fricke dosimetry for low energy X-Ray beam

NASA Astrophysics Data System (ADS)

Mantuano, A.; de Amorim, G. J.; David, M. G.; Rosado, P. H. G.; Salata, C.; Magalhães, L. A. G.; deAlmeida, C. E.

2018-03-01

The Fricke dosimeter is the most used, liquid chemical dosimeter. It has been shown to be a feasible option for the absorbed dose standard. The present work aims to determinate a dose-response curve of Fricke solution using different doses and reproducibility test comparing the calculated dose to Fricke solution and Ionizing Chamber. Tests were performed using an X-ray irradiator for biological research at Radiological Science Laboratory (LCR/UERJ). The results showed a linear response to different doses of type A uncertainties from 0.08 to 1.2%. Reproducibility test showed type A uncertainties of 0.16% to the dosimeter.

The role of gut microbiota in the regulation of standard metabolic rate in female Periplaneta americana.

PubMed

Ayayee, Paul A; Ondrejech, Andrew; Keeney, George; Muñoz-Garcia, Agustí

2018-01-01

Insect gut microbiota contribute significantly to host nutritional ecology. Disrupting insect gut microbial assemblages impacts nutrient provisioning functions, and can potentially affect host standard metabolic rate (SMR), a measure of host energy balance. In this study, we evaluated the effect of disrupting gut microbial assemblages on the SMR of female Periplaneta americana cockroaches fed dog food (DF, high protein/carbohydrate (p/c) ratio), and cellulose-amended dog food (CADF, 30% dog food, 70% cellulose, low p/c ratio) diets, supplemented with none, low, or high antibiotic doses. Bacterial loads decreased significantly between diet types ( P = 0.04) and across antibiotic doses ( P = 0.04). There was a significant diet type x antibiotic dose interaction on SMR of females on both diets ( P = 0.05) by the end of the seven-day experimental period. In CADF-fed females, SMR decreased linearly with decreasing bacterial load. However, SMR of DF-fed females on the low dose was significantly higher than those in the control and high dose groups. This is interpreted as a diet-dependent response by low dose DF-fed females to the loss of nutritional services provided by gut bacteria. Severe reductions in bacterial load at high doses reduced SMR of females on both diet types. This study provides insights into the potential role of gut bacteria as modulators of host energy expenditure under varying dietary conditions.

SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sayah, N; Weiss, E; Watkins, W

Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM);more » an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is recommended for dose mapping. Interpolative dose methods are sufficiently accurate for the majority of cases. J.V. Siebers receives funding support from Varian Medical Systems.« less

Improved statistical analysis of moclobemide dose effects on panic disorder treatment.

PubMed

Ross, Donald C; Klein, Donald F; Uhlenhuth, E H

2010-04-01

Clinical trials with several measurement occasions are frequently analyzed using only the last available observation as the dependent variable [last observation carried forward (LOCF)]. This ignores intermediate observations. We reanalyze, with complete data methods, a clinical trial previously reported using LOCF, comparing placebo and five dosage levels of moclobemide in the treatment of outpatients with panic disorder to illustrate the superiority of methods using repeated observations. We initially analyzed unprovoked and situational, major and minor attacks as the four dependent variables, by repeated measures maximum likelihood methods. The model included parameters for linear and curvilinear time trends and regression of measures during treatment on baseline measures. Significance tests using this method take into account the structure of the error covariance matrix. This makes the sphericity assumption irrelevant. Missingness is assumed to be unrelated to eventual outcome and the residuals are assumed to have a multivariate normal distribution. No differential treatment effects for limited attacks were found. Since similar results were obtained for both types of major attack, data for the two types of major attack were combined. Overall downward linear and negatively accelerated downward curvilinear time trends were found. There were highly significant treatment differences in the regression slopes of scores during treatment on baseline observations. For major attacks, all treatment groups improved over time. The flatter regression slopes, obtained with higher doses, indicated that higher doses result in uniformly lower attack rates regardless of initial severity. Lower doses do not lower the attack rate of severely ill patients to those achieved in the less severely ill. The clinical implication is that more severe patients require higher doses to attain best benefit. Further, the significance levels obtained by LOCF analyses were only in the 0.05-0.01 range, while significance levels of <0.00001 were obtained by these repeated measures analyses indicating increased power. The greater sensitivity to treatment effect of this complete data method is illustrated. To increase power, it is often recommended to increase sample size. However, this is often impractical since a major proportion of the cost per subject is due to the initial evaluation. Increasing the number of repeated observations increases power economically and also allows detailed longitudinal trajectory analyses.

Maternal dietary nitrate intake and risk of neural tube defects: A systematic review and dose-response meta-analysis.

PubMed

Kakavandi, Nader Rahimi; Hasanvand, Amin; Ghazi-Khansari, Mahmoud; Sezavar, Ahmad Habibian; Nabizadeh, Hassan; Parohan, Mohammad

2018-05-12

Despite growing evidence for the potential teratogenicity of nitrate, knowledge about the dose-response relationship of dietary nitrate intake and risk of specific birth defects such as neural tube defects (NTDs) is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the dose-response relation between maternal dietary nitrate intake and the risk of NTDs. We conducted a systematic search in PubMed, ISI Web of Science and Scopus up to February 2018 for observational studies. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a random-effects model for highest versus lowest intake categories. The linear and non-linear relationships between nitrate intake and risk of NTDs were also investigated. Overall, 5 studies were included in the meta-analyses. No association was observed between nitrate intake and NTDs risk in high versus low intake (RR: 1.33; 95% CI: 0.89-1.99, p = 0.158) and linear dose-response (RR: 1.03; 95% CI: 0.99-1.07, p = 0.141) meta-analysis. However, there were positive relationships between nitrate intake and risk of NTDs in non-linear (p non-linearity <0.05) model. Findings from this dose-response meta-analysis indicate that maternal nitrate intake higher than ∼3 mg/day is positively associated with NTDs risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells

PubMed Central

Jin, Xiaodong; Liu, Yan; Ye, Fei; Liu, Xiongxiong; Furusawa, Yoshiya; Wu, Qingfeng; Li, Feifei; Zheng, Xiaogang; Dai, Zhongying; Li, Qiang

2014-01-01

Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy. However, there is a little information currently available on the cellular and molecular basis for heavy-ion irradiation-induced cell death. Autophagy, as a novel important target to improve anticancer therapy, has recently attracted considerable attention. In this study, the effect of autophagy induced by high linear energy transfer (LET) carbon ions was examined in various tumor cell lines. To our knowledge, our study is the first to reveal that high-LET carbon ions could induce autophagy in various tumor cells effectively, and the autophagic level in the irradiated cells increased in a dose- and LET-dependent manner. The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of autophagy in tumor cells could modify their sensitivity to high-LET radiation, and inhibiting autophagy accelerated apoptotic cell death, resulting in an increase in radiosensitivity. Our data imply that targeting autophagy might enhance the effectiveness of heavy-ion radiotherapy. PMID:24731006

Energy-dependent RBE of neutrons to induce micronuclei in root-tip cells of Allium cepa onion irradiated as dry dormant seeds and seedlings.

PubMed

Zhang, Wenyi; Fujikawa, Kazuo; Endo, Satoru; Ishikawa, Masayori; Ohtaki, Megu; Ikeda, Hideo; Hoshi, Masaharu

2003-06-01

The relative biological effectiveness (RBE) of various energy neutrons produced from a Schenkel-type accelerator at the Research Institute for Radiation Biology and Medicine, Hiroshima University (HIRRAC), compared with 60Co gamma-ray radiation was determined. The neutron radiations and gamma-ray radiation produced good linear changes in the frequency of micronuclei induced in the root-tip cells of Allium cepa onion irradiated as dry dormant seeds (seed assay) and seedlings (seedling assay) with varying radiation doses. Therefore the RBE for radiation-induced micronuclei can be calculated as the ratio of the slopes of the fitted linear dose response for the neutron radiations and the 60Co gamma-ray radiation. The RBE values by seed assay and seedling assay decreased to 174 +/- 7, from 216 +/- 9, and to 31.4 +/- 1.0, from 45.3 +/- 1.3 (one standard error), respectively, when neutron energies increased to 1.0 MeV, from 0.2 MeV, in the present study. Furthermore, the ratio of the micronucleus induction rates of seed assay to seedling assay by gamma-ray radiation was much lower than that by neutron radiations.

Feasibility of RACT for 3D dose measurement and range verification in a water phantom.

PubMed

Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M

2015-02-01

The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly impact beam commissioning, treatment verification during particle beam therapy and image guided techniques.

Pupillography as a sensitive, noninvasive biomarker in healthy volunteers: first-in-man study of BAY 63-9044, a new 5-HT1A-receptor agonist with dopamine agonistic properties.

PubMed

Wensing, Georg; Haase, Claus; Brendel, Erich; Böttcher, Michael Friedrich

2007-12-01

BAY 63-9044 is a new full 5-HT(1A)-agonist with functional dopamine agonist properties aimed for the treatment of Parkinson's disease. This first-in-man study investigated the pharmacodynamics, safety and tolerability as well as the pharmacokinetics of BAY 63-9044 in a randomized, single-blind, placebo-controlled group-comparison dose escalation study. 45 healthy men received BAY 63-9044 as an oral solution in single doses of 0.25 mg, 0.5 mg, 1.2 mg, 2.5 mg and 5.0 mg. Pupil reaction (baseline pupil diameter (DIAM), constriction amplitude (CA)), body temperature, electroencephalography (EEG) and prolactin, cortisol and adrenocorticotrophic hormone (ACTH) served as pharmacodynamic measures and were monitored up to 24 h after drug intake. Safety, tolerability and plasma samples for determination of BAY 63-9044 were followed up to 72 h. Up to a dose of 2.5 mg, BAY 63-9044 was safe and well tolerated. Dose-limiting adverse events (nausea, vomiting, and dizziness) occurred in 5 out of 6 volunteers at the 5 mg dose. Adverse events resolved spontaneously in all but one volunteers who was treated with an antihistaminergic for vomiting. Dose-dependent changes of DIAM and CA were observed at doses higher than 0.5 mg and 1.2 mg, respectively. Body temperature showed a trend for reduction starting at C(max) in the highest two doses only. No clear effect was found on prolactin, cortisol and ACTH levels. The pharmacokinetics of BAY 63-9044 showed a dose-dependent increase with maximum plasma concentrations reached within 1 h. Plasma concentrations declined in a bi-phased manner with an apparent terminal half-life of 5.2-8.1 h. Up to the maximum tolerated dose (MTD) of 2.5 mg BAY 63-9044 was safe and well tolerated and showed predictable linear pharmacokinetics. Pupil reaction may serve as a non-invasive biomarker for pharmacodynamic effects of 5-HT(1A)-compounds with DIAM being the most sensitive parameter.

SU-F-T-329: Characteristic Study of a Rado-Photoluminescenct Glass Dosimeter with Accumulated Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, D; Chung, W; Chung, M

Purpose: This study investigated the effect of accumulated dose on radiophotoluminescent glass dosimeter in megavoltage photon. Methods: 45 commercially-available radio-photoluminescence glass dosimeters (RPLGD; GD-302M, Asahi Techno Glass Co., Shizuoka, JAPAN) were irradiated to 10 × 10 cm{sup 2} open-field with 6, 10 and 15 MV photon beams at 100 cm of source to surface distance and dose maximum depths. Each energy has consists of five groups which is consists of three detectors. A group #1 and #2 was irradiated about 1 Gy to 100 Gy, and estimated the integral dose response with and without annealing procedure. A group #3 wasmore » read the dose after irradiated 10 Gy of dose by 10 times repeatedly to estimate the fading effect of RPLGD. A group #4 and #5 was produced same ways with different irradiation dose such as 50 Gy for group #4 and 100 Gy for group #5. Results: From the results of group #1 and #2, an annealed detector shows linear response to integral dose but other detectors without the annealing process, has supra linearity for integral dose especially close to 100 Gy dose. For group #3, #4 and #5, the dose response of repeated irradiation, the dose response was decreased about 15%, 12% and 7% for 6 MV, 10 MV and 15MV. Conclusion: It was found that RPLGD response to accumulated dose was supra linear and this respond was altered with amount of accumulated dose to the RPLGD. In addition, the fading effect need to be concern with RPLGD.« less

TLD efficiency calculations for heavy ions: an analytical approach

DOE PAGES

Boscolo, Daria; Scifoni, Emanuele; Carlino, Antonio; ...

2015-12-18

The use of thermoluminescent dosimeters (TLDs) in heavy charged particles’ dosimetry is limited by their non-linear dose response curve and by their response dependence on the radiation quality. Thus, in order to use TLDs with particle beams, a model that can reproduce the behavior of these detectors under different conditions is needed. Here a new, simple and completely analytical algorithm for the calculation of the relative TL-efficiency depending on the ion charge Z and energy E is presented. In addition, the detector response is evaluated starting from the single ion case, where the computed effectiveness values have been compared withmore » experimental data as well as with predictions from a different method. The main advantage of this approach is that, being fully analytical, it is computationally fast and can be efficiently integrated into treatment planning verification tools. In conclusion, the calculated efficiency values have been then implemented in the treatment planning code TRiP98 and dose calculations on a macroscopic target irradiated with an extended carbon ion field have been performed and verified against experimental data.« less

Effect of initial microbial density on inactivation of Giardia muris by ozone.

PubMed

Haas, Charles N; Kaymak, Baris

2003-07-01

Inactivation of microorganisms by disinfectants frequently shows non-linear behavior on a semilogarithmic plot of log survival ratio versus time. A number of models have been developed to depict these deviations from Chick's Law. Some of the models predict that the log survival ratio (at a particular disinfectant dose and contact time, even in absence of demand) would be a function of the initial concentration of microorganisms (N(0)), while other models do not predict such an effect. The effect of N(0) on the survival ratio has not been deliberately tested. This work examined the inactivation of Giardia muris by ozone in batch systems, deliberately varying the disinfectant dose and N(0). It was found that the models predicting a dependency of survival on N(0) gave a better description to the data than models that did not predict such a dependency. Hence there is an apparent decrease in disinfection efficiency of ozone against Giardia muris (at pH 8 and 15 degrees C) as the initial microorganism concentration decreases. This phenomena should be taken into account by both disinfection researchers and by process design engineers.

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

PubMed Central

Bednarz, Bryan; Hancox, Cindy; Xu, X George

2012-01-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment. PMID:19671968

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

NASA Astrophysics Data System (ADS)

Bednarz, Bryan; Hancox, Cindy; Xu, X. George

2009-09-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment.

A new form of the calibration curve in radiochromic dosimetry. Properties and results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamponi, Matteo, E-mail: mtamponi@aslsassari.it; B

Purpose: This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. Methods: The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer–Lambert law and a simple modeling of the film. The new calibration curve hasmore » been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. Results: The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. Conclusions: The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.« less

A new form of the calibration curve in radiochromic dosimetry. Properties and results.

PubMed

Tamponi, Matteo; Bona, Rossana; Poggiu, Angela; Marini, Piergiorgio

2016-07-01

This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer-Lambert law and a simple modeling of the film. The new calibration curve has been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.

SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, D; Titt, U; Mirkovic, D

2016-06-15

Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Tian; Feng, Wei; Kuang, Dan

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects ofmore » these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P{sub interaction}≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. - Highlights: • Heavy metals and PAHs are predominate toxic constituents of particulate matters. • Urinary As and Ni showed linear dose-dependent effects on 8-OHdG and 8-iso-PGF2α. • PAHs significant interact with toxic metal in increasing 8-OHdG and 8-iso-PGF2α. • Co-exposure to high PAHs and toxic metals contribute to highest oxidative stress.« less

Nonclinical and clinical pharmacological characterization of the potent and selective cathepsin K inhibitor MIV-711.

PubMed

Lindström, Erik; Rizoska, Biljana; Henderson, Ian; Terelius, Ylva; Jerling, Markus; Edenius, Charlotte; Grabowska, Urszula

2018-05-09

Cathepsin K is an attractive therapeutic target for diseases in which bone resorption is excessive such as osteoporosis and osteoarthritis (OA). The current paper characterized the pharmacological profile of the potent and selective cathepsin K inhibitor, MIV-711, in vitro and in cynomolgus monkeys, and assessed translation to human based on a single dose clinical study in man. The potency and selectivity of MIV-711 were assessed in vitro using recombinant enzyme assays and differentiated human osteoclasts. MIV-711 was administered to healthy cynomolgus monkeys (3-30 µmol/kg, p.o.). Plasma levels of MIV-711 and the bone resorption biomarker CTX-I were measured after single dose experiments, and urine levels of CTX-I, NTX-I and CTX-II biomarkers were measured after repeat dose experiments. The safety, pharmacokinetics and pharmacodynamics (serum CTX-I) of MIV-711 were assessed in human healthy subjects after single ascending doses from 20 to 600 mg. MIV-711 was a potent inhibitor of human cathepsin K (K i : 0.98 nmol/L) with > 1300-fold selectivity towards other human cathepsins. MIV-711 inhibited human osteoclast-mediated bone resorption with an IC 50 value of 43 nmol/L. Single oral doses of MIV-711 to monkeys reduced plasma levels of CTX-I in a dose-dependent fashion by up to 57% at trough. The effect on CTX-I was linearly correlated to the plasma exposure of MIV-711, while the efficacy duration outlasted plasma exposure. Repeat oral dosing with MIV-711 also reduced urinary levels of the bone resorption biomarkers CTX-I (by 93%) and NTX-I (by 71%) and the cartilage degradation biomarker CTX-II (by 71%). MIV-711 was safe and well-tolerated when given as single ascending doses to healthy subjects. MIV-711 reduced serum CTX-I levels in a dose-dependent manner by up to 79% at trough. The relationship between MIV-711 exposure and effects on these biomarkers in humans was virtually identical when compared to the corresponding monkey data. MIV-711 is a potent and selective cathepsin K inhibitor with dose-dependent effects on biomarkers of bone and cartilage degradation in monkey and human. Taken together, MIV-711 shows promise for the treatment of bone and cartilage related disorders in humans, such as OA. Trial Registration EudraCT number 2011-003024-12, registered on June 22nd 2011.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

PubMed

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

General equations for optimal selection of diagnostic image acquisition parameters in clinical X-ray imaging.

PubMed

Zheng, Xiaoming

2017-12-01

The purpose of this work was to examine the effects of relationship functions between diagnostic image quality and radiation dose on the governing equations for image acquisition parameter variations in X-ray imaging. Various equations were derived for the optimal selection of peak kilovoltage (kVp) and exposure parameter (milliAmpere second, mAs) in computed tomography (CT), computed radiography (CR), and direct digital radiography. Logistic, logarithmic, and linear functions were employed to establish the relationship between radiation dose and diagnostic image quality. The radiation dose to the patient, as a function of image acquisition parameters (kVp, mAs) and patient size (d), was used in radiation dose and image quality optimization. Both logistic and logarithmic functions resulted in the same governing equation for optimal selection of image acquisition parameters using a dose efficiency index. For image quality as a linear function of radiation dose, the same governing equation was derived from the linear relationship. The general equations should be used in guiding clinical X-ray imaging through optimal selection of image acquisition parameters. The radiation dose to the patient could be reduced from current levels in medical X-ray imaging.

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

PubMed

Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

2008-01-01

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.

A Randomized Trial of Vitamin D3 Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

PubMed Central

Laing, E. M.; Hill Gallant, K. M.; Hall, D. B.; McCabe, G. P.; Hausman, D. B.; Martin, B. R.; Warden, S. J.; Peacock, M.; Weaver, C. M.

2013-01-01

Context: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. Objective: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Design: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. Results: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Conclusion: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children. PMID:24092833

Relative biologic effectiveness in terms of tumor response of {sup 125}I implants compared with {sup 60}Co gamma rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehnert, Shirley; Reniers, Brigitte; Verhaegen, Frank

2005-09-01

Purpose: To measure the relative biologic effectiveness (RBE) for {sup 125}I seeds compared with external beam radiotherapy using a clinically relevant in vivo system. Methods and Materials: Photon emission from a detailed source model was simulated using the Monte Carlo code MCNP4C, sampling from a {sup 125}I spectrum. The mouse RIF-1 tumor was treated with either temporary implant of an {sup 125}I seed or with {sup 60}Co gamma rays. The tumors were always the same size at the initiation of treatment, and the endpoint was growth inhibition. Results: The dose-response curve for both modalities was close to linear and wasmore » independent of the initial {sup 125}I activity (dose rate) for the range investigated. Calculation of the RBE for tumor response requires assigning a unique value for the tumor dose that is not homogenous but depends on the distance from the {sup 125}I source. Because tumor regrowth will depend on the subpopulation of cells that have the greatest probability of survival (i.e., those at the greatest distance from the {sup 125}I source), one approach is to use the dose to this population. On this basis, the RBE for {sup 125}I compared with {sup 60}Co gamma rays is 1.5. If the {sup 125}I dose is computed as the average dose to the tumor, corrected for the dose that is wasted as overkill in the cell population closest to the center of the {sup 125}I seed, the RBE is 1.4. Conclusion: The result, an RBE of 1.4-1.5 is similar to findings obtained by other methods, supporting the validity of this approach to derive an RBE with validity in a clinical context.« less

28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

NASA Astrophysics Data System (ADS)

Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-05-01

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

Characterization of a new unshielded diode for small field dosimetry under flattening filter free beams.

PubMed

Reggiori, Giacomo; Mancosu, Pietro; Suchowerska, Natalka; Lobefalo, Francesca; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta

2016-02-01

To characterize the performance of a new unshielded silicon diode (Razor-IBA) for dose measurements in small flattening filter free beams. The Razor has an active volume of 0.6 mm in diameter and 20 µm in length. The detector response stability in measured dose, dose rate, dose per pulse, and dark current were evaluated. The detector response in square fields (0.6-5.0 cm) was determined using PDD curves, axial beam profiles and output ratios. The performances were compared to that of the previously available SFD-IBA and PFD-IBA diodes. The Razor short term stability relative to the SFD was much improved (<±0.1% after 1.2 kGy). The linearity was <±1% (0.05-30 Gy range) and the dose rate dependence was <±0.5% (4-24 Gy/min range). The dose per pulse dependence was <±0.7% (0.08-0.21 cGy/pulse range). The PDDs measured with Razor and PFD differed <1%. A larger dark current was observed with increase in dose (0.0025 pA/Gy) compared to the SFD (0.0002 pA/Gy). This characteristic is attributed to an increased concentration of recombination centers. The beam profile showed good agreement with the SFD. Penumbra differences were <±0.3 mm relative to PFD, with a slight overestimation of the tails (<1%), due to the absence of diode shielding. Output ratios were in good agreement for fields up to 5 × 5 cm(2) (<1%). The Razor diode has the same spatial resolution and performance reliability as its predecessor (SFD), but exhibits the additional advantage of improved stability. These features make the Razor diode detector a good candidate for small field dosimetry. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study.

PubMed

Bondonno, Nicola P; Bondonno, Catherine P; Rich, Lisa; Mas, Emilie; Shinde, Sujata; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2016-07-01

Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550. © 2016 American Society for Nutrition.

A randomized trial of vitamin D₃ supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption.

PubMed

Lewis, R D; Laing, E M; Hill Gallant, K M; Hall, D B; McCabe, G P; Hausman, D B; Martin, B R; Warden, S J; Peacock, M; Weaver, C M

2013-12-01

Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D₃ in healthy children are unknown. Our objective was to examine the dose-response effects of supplemental vitamin D₃ on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D₃ (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope ⁴⁴Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)₂D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Large increases in serum 25(OH)D with vitamin D₃ supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Influence of the Integral Quality Monitor transmission detector on high energy photon beams: A multi-centre study.

PubMed

Casar, Bozidar; Pasler, Marlies; Wegener, Sonja; Hoffman, David; Talamonti, Cinzia; Qian, Jianguo; Mendez, Ignasi; Brojan, Denis; Perrin, Bruce; Kusters, Martijn; Canters, Richard; Pallotta, Stefania; Peterlin, Primoz

2017-09-01

The influence of the Integral Quality Monitor (IQM) transmission detector on photon beam properties was evaluated in a preclinical phase, using data from nine participating centres: (i) the change of beam quality (beam hardening), (ii) the influence on surface dose, and (iii) the attenuation of the IQM detector. For 6 different nominal photon energies (4 standard, 2 FFF) and square field sizes from 1×1cm 2 to 20×20cm 2 , the effect of IQM on beam quality was assessed from the PDD 20,10 values obtained from the percentage dose depth (PDD) curves, measured with and without IQM in the beam path. The change in surface dose with/without IQM was assessed for all available energies and field sizes from 4×4cm 2 to 20×20cm 2 . The transmission factor was calculated by means of measured absorbed dose at 10cm depth for all available energies and field sizes. (i) A small (0.11-0.53%) yet statistically significant beam hardening effect was observed, depending on photon beam energy. (ii) The increase in surface dose correlated with field size (p<0.01) for all photon energies except for 18MV. The change in surface dose was smaller than 3.3% in all cases except for the 20×20cm 2 field and 10MV FFF beam, where it reached 8.1%. (iii) For standard beams, transmission of the IQM showed a weak dependence on the field size, and a pronounced dependence on the beam energy (0.9412 for 6MV to 0.9578 for 18MV and 0.9440 for 6MV FFF; 0.9533 for 10MV FFF). The effects of the IQM detector on photon beam properties were found to be small yet statistically significant. The magnitudes of changes which were found justify treating IQM either as tray factors within the treatment planning system (TPS) for a particular energy or alternatively as modified outputs for specific beam energy of linear accelerators, which eases the introduction of the IQM into clinical practice. Copyright © 2017. Published by Elsevier GmbH.

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

PubMed

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

Out-of-field doses and neutron dose equivalents for electron beams from modern Varian and Elekta linear accelerators.

PubMed

Cardenas, Carlos E; Nitsch, Paige L; Kudchadker, Rajat J; Howell, Rebecca M; Kry, Stephen F

2016-07-08

Out-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases.

Cannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.

PubMed

Böcker, K B E; Gerritsen, J; Hunault, C C; Kruidenier, M; Mensinga, Tj T; Kenemans, J L

2010-07-01

Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America. Copyright 2010 Elsevier Inc. All rights reserved.

Effect of heavy-ion and electron irradiation on properties of Fe-based superconductors

NASA Astrophysics Data System (ADS)

Konczykowski, Marcin

2013-03-01

The introduction of defects by particle irradiation is used to reveal the role of disorder in matter, which is unavoidable in all crystalline solids. In superconductors defects introduce flux pinning, controlling critical current, Jc; as well as pair-breaking scattering, limiting the critical temperature, Tc. To elucidate defect related properties of Fe-based superconductors (FBS) we precede in two types of irradiation: heavy ion (6GeV Pb) to create disorder in the form of amorphous tracks and low temperature electron irradiation (2.5MeV at 20K) to create point like defects. Substantial increase of irreversible magnetization and an upward shift of the irreversibility line are observed after heavy ion irradiation of all FBS investigated to date. In BaK 122 , signatures of a Bose-glass vortex state; angular dependence and variable-range hopping flux creep are revealed. Remarkably, heavy ion irradiation does not depress Tc, however, point-like disorder introduced by electron irradiation does substantially. In isovalently substituted Ba(FeAs1 - xPx) 2 and Ba(Fe1 - x Rux As) 2 crystals, Tc decreases linearly with dose. Suppression to 40 % of initial value of Tc was achieved in Ba(FeAs1 - xPx) 2 . An increase of normal state resistivity is observed and correlated to depression of Tc. Change of superconducting gap structure with disorder was determined from penetration depth measurements, λ (T) dependence, at various stages of irradiation. Linear in T variation of pristine samples, indicative of the presence of nodes in gap, turned at low irradiation dose to exponential T variation, indicative of a fully gaped state. T2 variation of λ is observed at higher doses. This behaviour is incompatible with symmetry-imposed nodes of d-wave pairing but consistent with S + / - , S + / + mechanisms. This is the first observation of the impurity-induced node lifting expected in anisotropic s-wave superconductors

Indirect flat-panel detector with avalanche gain: Fundamental feasibility investigation for SHARP-AMFPI (scintillator HARP active matrix flat panel imager)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Wei; Li Dan; Reznik, Alla

2005-09-15

An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoidmore » pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d{sub Se} and the applied electric field E{sub Se} of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E{sub Se} dependence of both avalanche gain and optical quantum efficiency of an 8 {mu}m HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E{sub Se}: (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 {mu}m can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy.« less

Writing silica structures in liquid with scanning transmission electron microscopy.

PubMed

van de Put, Marcel W P; Carcouët, Camille C M C; Bomans, Paul H H; Friedrich, Heiner; de Jonge, Niels; Sommerdijk, Nico A J M

2015-02-04

Silica nanoparticles are imaged in solution with scanning transmission electron microscopy (STEM) using a liquid cell with silicon nitride (SiN) membrane windows. The STEM images reveal that silica structures are deposited in well-defined patches on the upper SiN membranes upon electron beam irradiation. The thickness of the deposits is linear with the applied electron dose. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) demonstrate that the deposited patches are a result of the merging of the original 20 nm-diameter nanoparticles, and that the related surface roughness depends on the electron dose rate used. Using this approach, sub-micrometer scale structures are written on the SiN in liquid by controlling the electron exposure as function of the lateral position. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorino, Claudio, E-mail: fiorino.claudio@hsr.it; Broggi, Sara; Fossati, Nicola

Purpose: To fit the individual biochemical recurrence-free survival (bRFS) data from patients treated with postprostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model. Methods and Materials: Considering pre-RT prostate-specific antigen (PSA) as a surrogate of the number of clonogens, bRFS may be expressed as a function of dose-per-fraction–dependent radiosensitivity (α{sub eff}), the number of clonogens for pre-RT PSA = 1 ng/mL (C), and the fraction of patients who relapse because of clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data from 894 node-negative, ≥pT2, pN0 hormone-naive patients treated withmore » adjuvant (n=331) or salvage (n=563) intent were available: 5-year bRFS data were fitted grouping patients according to GS (<7:392, =7:383, >7:119). Results: The median follow-up time, pre-RT PSA, and dose were 72 months, 0.25 ng/mL, and 66.6 Gy (range 59.4-77.4 Gy), respectively. The best-fit values were 0.23 to 0.26 Gy{sup −1} and 10{sup 7} for α{sub eff} and C for the model considering a linear dependence between K and PSA. Calibration plots showed good agreement between expected and observed incidences (slope: 0.90-0.93) and moderately high discriminative power (area under the curve [AUC]: 0.68-0.69). Cross-validation showed satisfactory results (average AUCs in the training/validation groups: 0.66-0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS. bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of the maximum) declined by about 2.7% and 4.5% for each increment of 0.1 ng/mL for GS <7 and ≥7, respectively. Conclusions: Individual data were fitted by a TCP model, and the resulting best-fit parameters were radiobiologically consistent. The model suggests that relapses frequently result from clonogens outside the irradiated volume, supporting the choice of lymph-node irradiation, systemic therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0 ng/mL; GS ≥7: PSA >0.3 ng/mL). Early RT should be preferred over delayed RT; the detrimental effect of PSA increase can never be fully compensated by increasing the dose, especially for patients with GS ≥7.« less

Effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells.

PubMed

Sun, Li; Wang, Xu

2003-09-01

To investigate the effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells. The gastric cancer SGC-7901 adenocarcinoma cells were treated with allicin and the cell cycle, inhibitory rate, apoptosis, telomerase activity and morphologic changes were studied by MTT assay, flow cytometry (FCM), TRAP-PCR-ELISA assay, light microscope, electron microscope respectively. Results were compared with that of AZT (3'-Azido-3'-deoxythymidine). SGC-7901 cells were suppressed after exposure to allicin of 0.016 mg/ml, 0.05 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P<0.05). Allicin could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G(2)/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P<0.05). Allicin could inhibit telomerase activity in a time-dependent and dose-dependent pattern. After exposure to allicin at 0.016 mg/ml for 24 hours, SGC-7901 cells showed typical morphologic change. Allicin can inhibit telomerase activity and induce apoptosis of gastric cancer SGC-7901 cells. Allicin may be more effective than AZT.

Assessing The Impact Of Cancer Therapies On Ovarian Reserve

PubMed Central

Gracia, Clarisa R.; Sammel, Mary D.; Freeman, Ellen; Prewitt, Maureen; Carlson, Claire; Ray, Anushree; Vance, Ashley; Ginsberg, Jill P.

2013-01-01

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, p<0.001; AFC: 14.55 vs. 27.20, p<0.001. In participants with an FSH<10, survivors had lower levels of AMH and AFC compared to controls. Alkylating agent dose score was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied. PMID:22137491

A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients.

PubMed

Tate, Sonya C; Sykes, Amanda K; Kulanthaivel, Palaniappan; Chan, Edward M; Turner, P Kellie; Cronier, Damien M

2018-03-01

Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modeling, and to evaluate target engagement at clinically relevant dose levels. A phase I study was conducted in cancer patients which incorporated intensive pharmacokinetic sampling after single and multiple oral doses of abemaciclib. Data were analyzed by popPK modeling, and patient demographics contributing to pharmacokinetic variability were explored. Target engagement was evaluated by combining the clinical popPK model with a previously developed pre-clinical pharmacokinetic/pharmacodynamic model. The pharmacokinetic analysis incorporated 4012 plasma concentrations from 224 patients treated with abemaciclib at doses ranging from 50 to 225 mg every 24 h and 75 to 275 mg every 12 h. A linear one-compartment model with time- and dose-dependent relative bioavailability (F rel ) adequately described the pharmacokinetics of abemaciclib. Serum albumin and alkaline phosphatase were the only significant covariates identified in the model, the inclusion of which reduced inter-individual variability in F rel by 10.3 percentage points. By combining the clinical popPK model with the previously developed pre-clinical pharmacokinetic/pharmacodynamic model, the extent of target engagement in skin in cancer patients was successfully predicted. The proportion of abemaciclib pharmacokinetic variability that can be attributed to patient demographics is negligible, and as such there are currently no dose adjustments recommended for adult patients of different sex, age, or body weight. NCT01394016 (ClinicalTrials.gov).

ESR dosimeter material properties of phenols compound exposed to radiotherapeutic electron beams

NASA Astrophysics Data System (ADS)

Gallo, Salvatore; Iacoviello, Giuseppina; Bartolotta, Antonio; Dondi, Daniele; Panzeca, Salvatore; Marrale, Maurizio

2017-09-01

There is a need for a sensitive dosimeter using Electron Spin Resonance spectroscopy for use in medical applications, since non-destructive read-out and dose archival could be achieved with this method. This work reports a systematic ESR investigation of IRGANOX ® 1076 exposed to clinical electron beams produced by a LINAC used for radiation therapy treatments. Recently, dosimetric features of this material were investigated for irradiation with 60Co γ -photons and neutrons in both pellet and film shape and have been found promising thanks to their high efficiency of radiation-matter energy transfer and radical stability at room temperature. Here the analysis of the dosimetric features of these ESR dosimeters exposed to clinical electron beams at energies of 7, 10 and 14 MeV, is described in terms of dependence on microwave power and modulation amplitude, response on dose, dependence on beam type, detection limits, and signal stability after irradiation. The analysis of the ESR signal as function of absorbed dose highlights that the response of this material is linear in the dose range investigated (1-13 Gy) and is independent of the beam energy. The minimum detectable dose is found to be smaller than 1 Gy. Comparison of electron stopping power values of these dosimeters with those of water and soft tissue highlights equivalence of the response to electron beams in the energy range considered. The signal intensity was monitored for 40 days after irradiation and for all energies considered and it shows negligible variations in the first 500 h after irradiation whereas after 1100 h the signal decay is only of about 4%. In conclusion, it is found that phenolic compounds possess good dosimetric features which make it useful as a sensitive dosimeter for medical applications.

A Semiempirical Approach to the Determination of Daily Erythemal Doses.

PubMed

Silva, Abel A; Yamamoto, Ana L C; Corrêa, Marcelo P

2018-02-15

The maintenance of ground-based instruments to measure the incidence of ultraviolet radiation (UVR) from the Sun demands strict and well-developed procedures. A piece of equipment can be out of service for a couple of weeks or months for calibration, repair or even the improvement of the facilities where it has been set up. However, the replacement of an instrument in such circumstances can be logistically and financially prohibitive. On the other hand, the lack of data can jeopardize a long-term experiment. In this study, we introduce a semiempirical approach to the determination of the theoretical daily erythemal dose (DED t ) for periods of instrumental absence in a tropical site. The approach is based on 5 years of ground-based measurements of daily erythemal dose (DED) linearly correlated with parameters of total ozone column (TOC) and reflectivity (R PC ) from the Ozone Monitoring Instrument (OMI) and the cosine of solar zenith angle at noon (SZA n ). Seventeen months of missing ground-based data were replaced with DED t , leading to a complete 5-year series of data. The lowest and the highest values of typical DED were 2411 ± 322 J m -2 (1σ) (winter) and 5263 ± 997 J m -2 (summer). The monthly integrated erythemal dose (mED) varied from 59 kJ m -2 (winter) to 162 kJ m -2 (summer). Both of them depended mainly on cos(SZA n ) and R PC . The 12-month integrated erythemal dose (12-ED) ranged from 1350 kJ m -2 to 1546 kJ m -2 , but it can depend significantly on other atmospheric parameter (maybe aerosols) not explicitly considered here. © 2018 The American Society of Photobiology.

A Monte Carlo approach to the microdosimetric kinetic model to account for dose rate time structure effects in ion beam therapy with application in treatment planning simulations.

PubMed

Manganaro, Lorenzo; Russo, Germano; Cirio, Roberto; Dalmasso, Federico; Giordanengo, Simona; Monaco, Vincenzo; Muraro, Silvia; Sacchi, Roberto; Vignati, Anna; Attili, Andrea

2017-04-01

Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study was to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for noninstantaneous intrafraction dose delivery or fractionation and comparing the effects of using different primary ions. An original formulation of the microdosimetric kinetic model (MKM) is used (named MCt-MKM), in which a Monte Carlo (MC) approach was introduced to account for the stochastic spatio-temporal correlations characteristic of the irradiations and the cellular repair kinetics. A modified version of the kinetic equations, validated on experimental cell survival in vitro data, was also introduced. The model, trained on the HSG cells, was used to evaluate the relative biological effectiveness (RBE) for treatments with acute and protracted fractions. Exemplary cases of prostate cancer irradiated with different ion beams were evaluated to assess the impact of the temporal effects. The LQ parameters for a range of cell lines (V79, HSG, and T1) and ion species (H, He, C, and Ne) were evaluated and compared with the experimental data available in the literature, with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET-dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion, and LET, exceeding up to 3% of the acute value in the case of a protraction in the delivery of 10 min. The intercomparison between different ions shows that the clinical optimality is strongly dependent on a complex interplay between the different physical and biological quantities considered. The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used. © 2017 American Association of Physicists in Medicine.

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with initiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1..mu..m. Abrahamson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will probably affect the ..beta.. component. 23 references, 5 figures, 2 tables.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberrration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with intiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1 ..mu..m. Abrahmson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will primarily affect the ..beta.. component, resulting in low assessments of interaction site diameters.« less

On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction.

PubMed

Crop, F; Van Rompaye, B; Paelinck, L; Vakaet, L; Thierens, H; De Wagter, C

2008-07-21

The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry.

Spinal cord protection during radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coia, L.; Chu, J.; Larsen, R.

1986-09-01

Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry anglemore » is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature.« less

Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus.

PubMed

Yu, Tian; Enioutina, Elena Y; Brunner, Hermine I; Vinks, Alexander A; Sherwin, Catherine M

2017-02-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with potentially severe clinical manifestation that mainly affects women of child-bearing age. Patients who do not respond to standard-of-care therapies, such as corticosteroids and immunosuppressants, require biologic therapeutics that specifically target a single or multiple SLE pathogenesis pathways. This review summarizes the clinical pharmacokinetic and pharmacodynamic characteristics of biologic agents that are approved, used off-label, or in the active pipeline of drug development for SLE patients. Depending on the type of target, the interacting biologics may exhibit linear (non-specific) or non-linear (target-mediated) disposition profiles, with terminal half-lives varying from approximately 1 week to 1 month. Biologics given by subcutaneous administration, which offers dosing flexibility over intravenous administration, demonstrated a relatively slow absorption with a time to maximum concentration of approximately 1 day to 2 weeks and a variable bioavailability of 30-82 %. The population pharmacokinetics of monoclonal antibodies were best described by a two-compartment model with central clearance and steady-state volume of distribution ranging from 0.176 to 0.215 L/day and 3.60-5.29 L, respectively. The between-subject variability in pharmacokinetic parameters were moderate (20-79 %) and could be partially explained by body size. The development of linked pharmacokinetic-pharmacodynamic models incorporating SLE disease biomarkers are an attractive strategy for use in dosing regimen simulation and optimization. The relationship between efficacy/adverse events and biologic concentration should be evaluated to improve clinical trial outcomes, especially for biologics in the advanced phase of drug development. New strategies, such as model-based precision dosing dashboards, could be utilized to incorporate information collected from therapeutic drug monitoring into pharmacokinetic/pharmacodynamic models to enable individualized dosing in real time.

Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

PubMed Central

Brussee, Janneke M.; Yeo, Tsin W.; Lampah, Daniel A.; Anstey, Nicholas M.

2015-01-01

Impaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria. PMID:26482311

A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

PubMed

Farese, Ann M; Cohen, Melanie V; Katz, Barry P; Smith, Cassandra P; Jackson, William; Cohen, Daniel M; MacVittie, Thomas J

2012-10-01

The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.

Response of Nanodot Optically Stimulated Luminescence Dosimeters to Therapeutic Electron Beams.

PubMed

Ponmalar, Y Retna; Manickam, Ravikumar; Sathiyan, S; Ganesh, K M; Arun, R; Godson, Henry Finlay

2017-01-01

Response of Al 2 O 3 :C-based nanoDot optically stimulated luminescence (OSL) dosimeter was studied for the dosimetry of 6, 9, 12, 16, and 20 MeV therapeutic electron beams. With reference to ionization chamber, no change in the response was observed with the change in the energy of electron beams for the field size from 6 cm × 6 cm to 25 cm × 25 cm, dose rates from 100 MU/min to 600 MU/min, and the linearity in the response up to 300 cGy. The fading of the transient signal was higher for 20 MeV electron beam than that of 6 MeV electron beam by about 5% as compared to value at 20 min after irradiation. The depletion of OSL signal per readout in 200 successive readouts was also found to change with dose and energy of electron beam from 6 MeV (9% and 12% per readout at 2 and 10 Gy, respectively) to 20 MeV (9% and 16% at 2 and 10 Gy, respectively). The OSL sensitivity changed in the range from 2% to 6% with accumulated doses from 2 to 8 Gy and with electron energy from 6 to 20 MeV, but the sensitivity could be reset using an optical annealing treatment. Although negligible fading for postirradiation storage from 20 min to several months, acceptable precision and linearity in the desired range, and high reproducibility makes nanoDot dosimeters very attractive for the dosimetry of therapeutic electron beams, a note should be made for changes in sensitivity at doses beyond 2 Gy and electron beams energy dependence in reuse, short-term fading, and signal depletion on repeated readout.

Response of Nanodot Optically Stimulated Luminescence Dosimeters to Therapeutic Electron Beams

PubMed Central

Ponmalar, Y. Retna; Manickam, Ravikumar; Sathiyan, S.; Ganesh, K. M.; Arun, R.; Godson, Henry Finlay

2017-01-01

Response of Al2O3:C-based nanoDot optically stimulated luminescence (OSL) dosimeter was studied for the dosimetry of 6, 9, 12, 16, and 20 MeV therapeutic electron beams. With reference to ionization chamber, no change in the response was observed with the change in the energy of electron beams for the field size from 6 cm × 6 cm to 25 cm × 25 cm, dose rates from 100 MU/min to 600 MU/min, and the linearity in the response up to 300 cGy. The fading of the transient signal was higher for 20 MeV electron beam than that of 6 MeV electron beam by about 5% as compared to value at 20 min after irradiation. The depletion of OSL signal per readout in 200 successive readouts was also found to change with dose and energy of electron beam from 6 MeV (9% and 12% per readout at 2 and 10 Gy, respectively) to 20 MeV (9% and 16% at 2 and 10 Gy, respectively). The OSL sensitivity changed in the range from 2% to 6% with accumulated doses from 2 to 8 Gy and with electron energy from 6 to 20 MeV, but the sensitivity could be reset using an optical annealing treatment. Although negligible fading for postirradiation storage from 20 min to several months, acceptable precision and linearity in the desired range, and high reproducibility makes nanoDot dosimeters very attractive for the dosimetry of therapeutic electron beams, a note should be made for changes in sensitivity at doses beyond 2 Gy and electron beams energy dependence in reuse, short-term fading, and signal depletion on repeated readout. PMID:28405107

Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

PubMed

Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

2016-05-01

The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P < 0.05), indicating the systemic availability of MMS; however, the N7MeG DNA adduct, a target exposure biomarker, exhibited a non-linear dose-response in blood and liver tissues. Blood reticulocyte micronuclei (MN), a genotoxic effect biomarker, exhibited a clear no-observed-genotoxic-effect-level (NOGEL) of 5 mkd as a point of departure (PoD) for MMS. Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction. Liver gene expression, a mechanistic endpoint, also exhibited a bilinear dose-response. Similarly, in MNU-treated rats, hepatic DNA adducts, gene expression changes and MN all exhibited clear PoDs, with a NOGEL of 1 mkd for MN induction, although dose-response modeling of the MNU-induced MN data showed a better statistical fit for a linear dose-response. In summary, these results provide in vivo data that support the existence of clear non-linear dose-responses for a number of biologically significant events along the pathway for genotoxicity induced by DNA-reactive agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An approach to assessing stochastic radiogenic risk in medical imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolbarst, Anthony B.; Hendee, William R.; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55901

2011-12-15

Purpose: This letter suggests a formalism, the medical effective dose (MED), that is suitable for assessing stochastic radiogenic risks in diagnostic medical procedures. Methods: The MED is derived from radiobiological and probabilistic first principals, including: (1) The independence of radiation-induced biological effects in neighboring voxels at low doses; (2) the linear no-threshold assumption for stochastic radiation injury (although other dose-response relationships could be incorporated, instead); (3) the best human radiation dose-response data currently available; and (4) the built-in possibility that the carcinogenic risk to an irradiated organ may depend on its volume. The MED involves a dose-risk summation over irradiatedmore » voxels at high spatial resolution; it reduces to the traditional effective dose when every organ is irradiated uniformly and when the dependence of risk on organ volumes is ignored. Standard relative-risk tissue weighting factors can be used with the MED approach until more refined data become available. Results: The MED is intended for clinical and phantom dosimetry, and it provides an estimate of overall relative radiogenic stochastic risk for any given dose distribution. A result of the MED derivation is that the stochastic risk may increase with the volume of tissue (i.e., the number of cells) irradiated, a feature that can be activated when forthcoming radiobiological research warrants it. In this regard, the MED resembles neither the standard effective dose (E) nor the CT dose index (CTDI), but it is somewhat like the CT dose-length product (DLP). Conclusions: The MED is a novel, probabilistically and biologically based means of estimating stochastic-risk-weighted doses associated with medical imaging. Built in, ab initio, is the ability to link radiogenic risk to organ volume and other clinical factors. It is straightforward to implement when medical dose distributions are available, provided that one is content, for the time being, to accept the relative tissue weighting factors published by the International Commission of Radiological Protection (ICRP). It requires no new radiobiological data and avoids major problems encountered by the E, CTDI, and CT-E formalisms. It makes possible relative inter-patient dosimetry, and also realistic intercomparisons of stochastic risks from different protocols that yield images of comparable quality.« less

A mathematical deconvolution formulation for superficial dose distribution measurement by Cerenkov light dosimetry.

PubMed

Brost, Eric Edward; Watanabe, Yoichi

2018-06-01

Cerenkov photons are created by high-energy radiation beams used for radiation therapy. In this study, we developed a Cerenkov light dosimetry technique to obtain a two-dimensional dose distribution in a superficial region of medium from the images of Cerenkov photons by using a deconvolution method. An integral equation was derived to represent the Cerenkov photon image acquired by a camera for a given incident high-energy photon beam by using convolution kernels. Subsequently, an equation relating the planar dose at a depth to a Cerenkov photon image using the well-known relationship between the incident beam fluence and the dose distribution in a medium was obtained. The final equation contained a convolution kernel called the Cerenkov dose scatter function (CDSF). The CDSF function was obtained by deconvolving the Cerenkov scatter function (CSF) with the dose scatter function (DSF). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) Monte Carlo particle simulation software was used to obtain the CSF and DSF. The dose distribution was calculated from the Cerenkov photon intensity data using an iterative deconvolution method with the CDSF. The theoretical formulation was experimentally evaluated by using an optical phantom irradiated by high-energy photon beams. The intensity of the deconvolved Cerenkov photon image showed linear dependence on the dose rate and the photon beam energy. The relative intensity showed a field size dependence similar to the beam output factor. Deconvolved Cerenkov images showed improvement in dose profiles compared with the raw image data. In particular, the deconvolution significantly improved the agreement in the high dose gradient region, such as in the penumbra. Deconvolution with a single iteration was found to provide the most accurate solution of the dose. Two-dimensional dose distributions of the deconvolved Cerenkov images agreed well with the reference distributions for both square fields and a multileaf collimator (MLC) defined, irregularly shaped field. The proposed technique improved the accuracy of the Cerenkov photon dosimetry in the penumbra region. The results of this study showed initial validation of the deconvolution method for beam profile measurements in a homogeneous media. The new formulation accounted for the physical processes of Cerenkov photon transport in the medium more accurately than previously published methods. © 2018 American Association of Physicists in Medicine.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study.

PubMed

Slingsby, L S; Taylor, P M

2008-04-01

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups (n = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 microg/kg; positive and negative controls were administered buprenorphine (20 microg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey's tests (P < 0.05). Only dexmedetomidine at 40 microg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 microg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose-dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.

Search for the effect of E-beam irradiation on some steroids

NASA Astrophysics Data System (ADS)

Marciniec, B.; Ogrodowczyk, M.; Dettlaff, K.

2005-03-01

Seven steroid derivatives (hydrocortisone, hydrocortisone acetate, prednisolone, prednisolone acetate, methylprednisolone acetate, dexamethasone and fludrocortisone acetate) irradiated in the solid phase 10 MeV electrons, were studied by chromatographic methods (TLC and HPLC). Before the irradiation the derivatives contained different amounts of the following impurities: cortisone, cortisone acetate, prednisolone, prednisolone acetate and prednisone. After irradiation with a dose of upto 200 kGy radiolytic products were identified: cortisone, cortisone acetate, prednisone, prednisolone and methylprednisone acetate. All the identified radiolytic products were formed as a result of oxidation of the substituent at C 11, and in some cases the oxidation was accompanied by cleavage of the ester bond. The content of impurities before irradiation did not exceed 0.8%, while after the irradiation the content of the products of radiolysis depended on the kind of the derivative and the dose, and varied from 0.6% for a dose of 25 kGy to 4.03% for a dose of 200 kGy. For some derivatives, a linear relationship was found between the loss of a given steroid content and the dose. The studied steroid derivatives are characterised by high radiochemical stability and their sterilisation by irradiation does not lead to loss of the active substance below 97%, i.e. the lower limit admissible by the pharmacopoeias.

Neonatal outcomes following exposure in utero to fallout from Chernobyl.

PubMed

Hatch, Maureen; Little, Mark P; Brenner, Alina V; Cahoon, Elizabeth K; Tereshchenko, Valery; Chaikovska, Ludmyla; Pasteur, Igor; Likhtarov, Ilya; Bouville, Andre; Shpak, Victor; Bolshova, Olena; Zamotayeva, Galyna; Grantz, Katherine; Sun, Liping; Mabuchi, Kiyohiko; Albert, Paul; Tronko, Mykola

2017-12-01

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (-1.0 cm/Gy, P = 0.005) and chest circumference (-0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (-0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

PubMed

Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

2017-05-10

Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Measuring trends of outpatient antibiotic use in Europe: jointly modelling longitudinal data in defined daily doses and packages.

PubMed

Bruyndonckx, Robin; Hens, Niel; Aerts, Marc; Goossens, Herman; Molenberghs, Geert; Coenen, Samuel

2014-07-01

To complement analyses of the linear trend and seasonal fluctuation of European outpatient antibiotic use expressed in defined daily doses (DDD) by analyses of data in packages, to assess the agreement between both measures and to study changes in the number of DDD per package over time. Data on outpatient antibiotic use, aggregated at the level of the active substance (WHO version 2011) were collected from 2000 to 2007 for 31 countries and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Data expressed in DID and PID were analysed separately using non-linear mixed models while the agreement between these measurements was analysed through a joint non-linear mixed model. The change in DDD per package over time was studied with a linear mixed model. Total outpatient antibiotic and penicillin use in Europe and their seasonal fluctuation significantly increased in DID, but not in PID. The use of combinations of penicillins significantly increased in DID and in PID. Broad-spectrum penicillin use did not increase significantly in DID and decreased significantly in PID. For all but one subgroup, country-specific deviations moved in the same direction whether measured in DID or PID. The correlations are not perfect. The DDD per package increased significantly over time for all but one subgroup. Outpatient antibiotic use in Europe shows contrasting trends, depending on whether DID or PID is used as the measure. The increase of the DDD per package corroborates the recommendation to adopt PID to monitor outpatient antibiotic use in Europe. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

Biodosimetry estimate for high-LET irradiation.

PubMed

Wang, Z Z; Li, W J; Zhi, D J; Jing, X G; Wei, W; Gao, Q X; Liu, B

2007-08-01

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV microm(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

Regulatory implications of a linear non-threshold (LNT) dose-based risks.

PubMed

Aleta, C R

2009-01-01

Current radiation protection regulatory limits are based on the linear non-threshold (LNT) theory using health data from atomic bombing survivors. Studies in recent years sparked debate on the validity of the theory, especially at low doses. The present LNT overestimates radiation risks since the dosimetry included only acute gammas and neutrons; the role of other bomb-caused factors, e.g. fallout, induced radioactivity, thermal radiation (UVR), electromagnetic pulse (EMP), and blast, were excluded. Studies are proposed to improve the dose-response relationship.