Post-irradiation Response Research Articles

An LTspice Simulation Model of Gamma-radiation Effects and Annealing in a Voltage Regulator With a Lateral Serial PNP Transistor With Round Emitters

The aim of this paper was to determine the reasons for a complex radiation response of the commercial-off-the-shelf LM2940CT5 low-dropout voltage regulator. Examination of this circuit in a gamma-radiation environment disqualified its use when operated with relatively high output currents, while its radiation tolerance was satisfactory when load current was approximately one-tenth (or lower) of the nominal value. In order to obtain a more thorough insight into the radiation response of this integrated circuit, a detailed SPICE model was developed. This model enabled mutual comparison of the influence of serial and driver PNP power transistor parameters: forward emitter current gain, knee current and emitter resistance. The serial lateral PNP power transistor with round emitters was identified as the weakest element that crucially affected the entire circuit radiation tolerance. The effects of gamma-radiation were examined for total doses up to 500 Gy followed by three sequences of isothermal annealing. Detailed characteristics of Beta(Ic) were procured for four different kinds of bias and load conditions during irradiation. The emitter resistance increase of the serial power transistor was a primary reason for the low radiation tolerance of the entire voltage regulator; it was much more influential than the perceived decline of the PNP power transistor forward emitter current gain. The influence of bias and load conditions were analysed with buildup of interface traps and the oxide-trapped charge, which affected the radiation and post-irradiation response of the serial power transistor.

Evaluating Magnetic Resonance Spectroscopy as a Tool for Monitoring Therapeutic Response of Whole Brain Radiotherapy in a Mouse Model for Breast-to-Brain Metastasis.

Brain metastases are the most common intracranial tumor in adults and are associated with poor patient prognosis and median survival of only a few months. Treatment options for brain metastasis patients remain limited and largely depend on surgical resection, radio- and/or chemotherapy. The development and pre-clinical testing of novel therapeutic strategies require reliable experimental models and diagnostic tools that closely mimic technologies that are used in the clinic and reflect histopathological and biochemical changes that distinguish tumor progression from therapeutic response. In this study, we sought to test the applicability of magnetic resonance (MR) spectroscopy in combination with MR imaging to closely monitor therapeutic efficacy in a breast-to-brain metastasis model. Given the importance of radiotherapy as the standard of care for the majority of brain metastases patients, we chose to monitor the post-irradiation response by magnetic resonance spectroscopy (MRS) in combination with MR imaging (MRI) using a 7 Tesla small animal scanner. Radiation was applied as whole brain radiotherapy (WBRT) using the image-guided Small Animal Radiation Research Platform (SARRP). Here we describe alterations in different metabolites, including creatine and N-acetylaspartate, that are characteristic for brain metastases progression and lactate, which indicates hypoxia, while choline levels remained stable. Radiotherapy resulted in normalization of metabolite levels indicating tumor stasis or regression in response to treatment. Our data indicate that the use of MR spectroscopy in addition to MRI represents a valuable tool to closely monitor not only volumetrical but also metabolic changes during tumor progression and to evaluate therapeutic efficacy of intervention strategies. Adapting the analytical technology in brain metastasis models to those used in clinical settings will increase the translational significance of experimental evaluation and thus contribute to the advancement of pre-clinical assessment of novel therapeutic strategies to improve treatment options for brain metastases patients.

2017 Michael Fry Award Lecture When DNA is Actually Not a Target: Radiation Epigenetics as a Tool to Understand and Control Cellular Response to Ionizing Radiation.

Aside from the generally accepted potential to cause DNA damage, it is becoming increasingly recognized that ionizing radiation has the capability to target the cellular epigenome. Epigenetics unifies the chemical marks and molecules that collectively facilitate the proper reading of genetic material. Among the epigenetic mechanisms of regulation, methylation of DNA is known to be the key player in the postirradiation response by controlling the expression of genetic information and activity of transposable elements. Radiation-induced alterations to DNA methylation may lead to cellular epigenetic reprogramming that, in turn, can substantially compromise the genomic integrity and has been proposed as one of the mechanisms of radiation-induced carcinogenesis. DNA methylation is strongly dependent on the one-carbon metabolism. This metabolic pathway is central to the support of DNA methylation by means of providing the donor of methyl groups, as well as for the synthesis of amino acids. To better understand the mechanisms of radiation-induced health effects, we study how exposure to radiation affects DNA methylation and one-carbon metabolism. Also, a tight interaction that exists between DNA methylation and one-carbon metabolism allows us to simultaneously manipulate both cellular epigenetic and metabolic profiles to modulate the normal and cancerous tissue response to radiotherapy.

Host mediated inflammatory influence on glioblastoma multiforme recurrence following high-dose ionizing radiation.

Despite optimal clinical treatment, glioblastoma multiforme (GBM) inevitably recurs. Standard treatment of GBM, exposes patients to radiation which kills tumor cells, but also modulates the molecular fingerprint of any surviving tumor cells and the cross-talk between those cells and the host. Considerable investigation of short-term (hours to days) post-irradiation tumor cell response has been undertaken, yet long-term responses (weeks to months) which are potentially even more informative of recurrence, have been largely overlooked. To better understand the potential of these processes to reshape tumor regrowth, molecular studies in conjunction with in silico modeling were used to examine short- and long-term growth dynamics. Despite survival of 2.55% and 0.009% following 8 or 16Gy, GBM cell populations in vitro showed a robust escape from cellular extinction and a return to pre-irradiated growth rates with no changes in long-term population doublings. In contrast, these same irradiated GBM cell populations injected in vivo elicited tumors which displayed significantly suppressed growth rates compared to their pre-irradiated counterparts. Transcriptome analysis days to weeks after irradiation revealed, 281 differentially expressed genes with a robust increase for cytokines, histones and C-C or C-X-C motif chemokines in irradiated cells. Strikingly, this same inflammatory signature in vivo for IL1A, CXCL1, IL6 and IL8 was increased in xenografts months after irradiation. Computational modeling of tumor cell dynamics indicated a host-mediated negative pressure on the surviving cells was a source of inhibition consistent with the findings resulting in suppressed tumor growth. Thus, tumor cells surviving irradiation may shift the landscape of population doubling through inflammatory mediators interacting with the host in a way that impacts tumor recurrence and affects the efficacy of subsequent therapies. Clues to more effective therapies may lie in the development and use of pre-clinical models of post-treatment response to target the source of inflammatory mediators that significantly alter cellular dynamics and molecular pathways in the early stages of tumor recurrence.

Solar disinfection modeling and post-irradiation response of Escherichia coli in wastewater

In this work, an intensive assessment of solar disinfection of secondary wastewater was elaborated in controlled laboratory conditions. Batch tests of Escherichia coli-spiked synthetic secondary effluent, at nine different constant intensity levels, were followed by a 48-h dark storage. Solar disinfection was monitored in half-hourly intervals demonstrating distinct phases of lag followed by sharp inactivation. The results were fit to a shoulder log-linear and a Weibull distribution model. The solar-driven inactivation, the latency period and the effective disinfection time (for 4-log reduction) were correlated properly with the applied irradiance, resulting in a common, standardized dose for all intensities. Evolution of bacterial response in the dark was monitored for 48h, and was in each case characterized as growth or decay. Also, the energy threshold, which was able to shift post-irradiation behavior from growth to decay, was analytically studied. In all intensity levels, this standard was approximately constant, as an effective bacteriostatic dose (EBD). Finally, similar dose-related disinfection and regrowth effects were observed, suggesting compliance with the reciprocity law, with minor deviations.

Transient and Post-irradiation Response of Optoelectronic Devices to Ionizing Radiation

Space and ground level electronic equipment with semiconductor devices are subjected to the deleterious effects by radiation. This paper is attempted to present the transient and post-irradiation response of optoelectronic devices to gamma (γ) rays utilizing cobalt-60. In situ measurements were made on the devices under test (DUTs) up to a total dose of 60 krad followed by a post-irradiation not in-flux test for eight hours. Current transfer ratio (CTR) with is the vital merit of the optoelectronic system is found to decrease remarkably with the absorbed dose. This degradation is induced by the interaction of the energetic photons from gamma rays via two main mechanisms. The dominant effect is the mechanism by ionization while the secondary is by displacement. This radiation effect is found to arouse either a permanent or temporarily damage in the DUTs depending on their current drives and also the Total Ionizing Dose (TID) absorbed. The TID effects by gamma rays are cumulative and gradually take place throughout the lifecycle of the devices exposed to radiation. The full damage cascade phenomenon in the DUTs is calculated via the simulation.

Study of the dose response of the system ferrous ammonium sulfate–sucrose–xylenol orange in acid aqueous solution

Abstract An aqueous solution of ammonium ferrous sulfate–sucrose–xylenol orange in sulfuric acid (FSX) is proposed as a dosimetric system for the processes of gamma irradiation in a range between 0.3 and 6 Gy. This system is based on the indirect oxidation of ferrous ion by an organic compound (sucrose) to ferric ion and on the formation of a color complex of Fe 3+ in an acidic medium with xylenol orange (a dye). After gamma radiation, an observable change occurs in the color of the system. Irradiation was executed at three different temperatures (13 °C, 22 °C, and 40 °C). A spectrometric readout method at 585 nm was employed to evaluate the system׳s dose response. In all of the cases analyzed, the responses had a linear behavior, and a slight effect of irradiation temperature was observed. Post-irradiation response was also evaluated and showed the stability of the solutions 24 h after the irradiation. The results obtained suggest that FSX might be used as a dosimeter for low doses of gamma irradiation because it provides a stable signal, good reproducibility, and an accessible technique for analysis.

Evaluation of various polyethylene as potential dosimeters by attenuated total reflectance-Fourier-transform infrared spectroscopy

Abstract Various types of polyethylene (PE) have been evaluated in the past for use as a potential dosimeter, chiefly via the formation of an unsaturated transvinylene (TV) double-bond resulting from exposure to ionizing radiation. The utilization of attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy in characterizing TV formation in irradiated PE for a potential dosimeter has yet to be fully developed. In this initial investigation, various PE films/sheets were exposed to ionizing radiation in a high-energy 5 megaelectron volt (MeV) electron beam accelerator in the 10–500 kilogray (kGy) dose range, followed by ATR-FTIR analysis of TV peak formation at the 965 cm −1 wavenumber. There was an upward trend in TV formation for low-density polyethylene (LDPE) films and high-density polyethylene (HDPE) sheets as a function of absorbed dose in the 10–50 kGy dose range, however, the TV response could not be equated to a specific absorbed dose. LDPE film displayed a downward trend from 50 kGy to 250 kGy and then scattering up to 500 kGy; HDPE sheets demonstrated an upward trend in TV formation up to 500 kGy. For ultra-high molecular weight polyethylene (UHMWPE) sheets irradiated up to 150 kGy, TV response was equivalent to non-irradiated UHMWPE, and a minimal upward trend was observed for 200 kGy to 500 kGy. The scatter of the data for the irradiated PE films/sheets is such that the TV response could not be equated to a specific absorbed dose. A better correlation of the post-irradiation TV response to absorbed dose may be attained through a better understanding of variables.

Contribution of fixed oxide traps to sensitivity of pMOS dosimeters during gamma ray irradiation and annealing at room and elevated temperature

Gamma-ray irradiation and post-irradiation response at room and elevated temperature of radiation sensitive p-channel MOS transistors have been studied. The response was observed on the basis of threshold voltage shift determined from transistors transfer characteristics. These characteristics together with charge-pumping characteristics proved to be useful in providing a detailed insight into the processes that occur during gamma-ray irradiation and subsequent annealing at room temperature and later at elevated temperature. In particular, the influence of fixed oxide traps, switching oxide traps (known as slow switching traps) and switching traps at Si/SiO 2 interface (known as fast switching traps) on threshold voltage shift has been analyzed.

Gamma-ray irradiation and post-irradiation at room and elevated temperature response of pMOS dosimeters with thick gate oxides

Gamma-ray irradiation and post-irradiation response at room and elevated temperature have been studied for radiation sensitive pMOS transistors with gate oxide thickness of 100 and 400 nm, respectively. Their response was followed based on the changes in the threshold voltage shift which was estimated on the basis of transfer characteristics in saturation. The presence of radiation-induced fixed oxide traps and switching traps - which lead to a change in the threshold voltage - was estimated from the sub-threshold I-V curves, using the midgap technique. It was shown that fixed oxide traps have a dominant influence on the change in the threshold voltage shift during gamma-ray irradiation and annealing.

Effect of Low Fluence Diode Laser Irradiation on the Hydraulic Conductivity of Perfused Trabecular Meshwork Endothelial Cell Monolayers

Objective: To determine the effect of low-fluence diode laser irradiation upon the fluid perfusion characteristics of cultured human trabecular meshwork cell monolayers when placed in a specially designed testing apparatus and subjected to fluid flow driven by a hydrostatic pressure gradient. Methods: Two experimental series were conducted. In the first series, six low-fluence diode laser irradiation experiments were conducted using cultured human trabecular meshwork cell monolayers grown on filter supports. Upon reaching a steady state perfusion condition at approximately 5.0 mmHg, monolayers were irradiated at fluencies ranging from 0.2619 to 0.8571 J/cm2 using a diode laser (λ = 810 nm). Perfusion and data collection continued for 45 minutes post-irradiation, after which the monolayers were tested to determine post-experimental viability. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5-minute intervals, grouped by viability. In the second series, a total of six irradiated experiments and six simulataneous nonirradiated control experiments were conducted. Fluence values of 0.3571 J/cm2 (n = 3) and 0.4286 J/cm2 (n = 3) were used. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5-minute intervals, grouped by irradiated vs. nonirradiated control groups. Results: In the first series, analysis showed that the viable monolayers exhibited a statistically significant increase in hydraulic conductivity (p < 0.001) from 10 minutes post-irradiation onward. The non-viable monolayers exhibited a statistically significant decrease in hydraulic conductivity. In the second series, irradiated groups showed a significant difference (p < 0.001) from nonirradiated controls from 10 minutes post-irradiation onward. Conclusion: Low-fluence diode laser irradiation increases hydraulic conductivity in viable perfused TM cell monolayers when compared to baseline values or simultaneous nonirradiated controls while decreasing hydraulic conductivity in nonviable monolayers.

Technical performance of the Luxel Al2O3:C optically stimulated luminescence dosemeter element at radiation oncology and nuclear accident dose levels

The dose ranges typical for radiation oncology and nuclear accident dosimetry are on the order of 2-70 Gy and 0.1-5 Gy, respectively. In terms of solid-state passive dosimetry, thermoluminescent (TL) materials historically have been used extensively for these two applications, with silver-halide, leuco-dye and BaFBr:Eu-based films being used on a more limited basis than TL for radiation oncology. This present work provides results on the performance of a film based on an aluminum oxide, Al(2)O(3):C, for these dosimetry applications, using the optically stimulated luminescence (OSL) readout method. There have been few investigations of Al(2)O(3):C performance at radiation oncology and nuclear accident dose levels, and these have included minimal dosimetric and environmental effects information. Based on investigations already published, the authors of this present study determined that overall improvements over film and TLDs for this Al(2)O(3):C OSL technology at radiation oncology and nuclear accident dose levels may include (1) a more tissue-equivalent response to photons compared to X-ray film, (2) higher sensitivity, (3) ability to reread dosemeters and (4) diagnostic capability using small-area imaging. The results of the present investigation indicate that additional favourable performance characteristics for the Al(2)O(3):C dosemeter are a wide dynamic range (0.001-100 Gy), a response insensitive to temperature and moisture over a wide range, negligible dose rate dependence, and minimal change in post-irradiation response. As a radiation detection medium, this OSL phosphor offers an assortment of dosimetry properties that will permit it to compete with current radiation detection technologies such as silver-halide, leuco-dye and photostimulable-phosphor-based films, as well as TLDs.

Implications of Characterization Temperature on Hardness Assurance Qualification

To explore the impact of temperature on the post-irradiation response of ICs, we characterized the temperature response of transistors, SRAMs, and a custom mixed-signal ASIC. Devices were irradiated at room temperature and electrically characterized post irradiation as a function of temperature. Devices exhibit significantly more parametric degradation when characterized at elevated temperatures. In addition to parametric degradation, it is demonstrated that post-irradiation elevated temperature characterization can also induce functional failures at significantly lower total dose levels than at room temperature. As a result, to ensure system functionality, it is essential that devices be characterized over the full system temperature range pre- and post-irradiation. Recommendations for incorporating temperature testing into a hardness assurance test method (i.e., Method 1019) are suggested. Methods for minimizing the detrimental effects of elevated temperature anneals on hardness assurance testing are also discussed

SU-FF-T-239: Enhanced Performance of PRESAGE - Sensitivity, and Post-Irradiation Stability

Purpose: To improve the dose sensitivity and to control the post-irradiation radiochromic response of PRESAGE™ a 3D dosimeter. Method and Materials: One cm plastic cuvettes were filled with formulations of PRESAGE™ that varied in the composition of leuco malachite green (LMG), a radical activator and a dissolution solvent. The dosimeters were irradiated using a Varian 600C linear accelarator with a 4 MV photon beam. The dosimeters were irradiated at doses ranging from 10cGy to 60 Gy (250 cGy/min) and measured on a Hitachi-Perkin Elmer 204 spectrometer at 630 nm. The absorbances were measured 10 minutes after irradiation and up to a week post-irradiation. The sensitivity of PRESAGE™ to room light was investigated by placing dosimeters in a laboratory under constant room light at 22°C for approximately 6 hr and periodically measuring the radiochromic response. Results: The radiochromic response at 630 nm was linear from 0 to approximately 30 Gy with a slope of 0.16 OD/Gy and with an error, R2, of 0.9995. The lower limit of dose measurement of the dosimeter is 10cGy. The stability of the post-irradiation radiochromic response can be varied with minor detectable radiochromic response loss after 7 days (<1%/24 hr) to nearly 100% loss of radiochromic response 24 hr. When exposed to room light the photochromic background increases 0.05 cm−1/ hr. Conclusion: The performance characteristics of PRESAGE™ have been enhanced by increasing the sensitivity of the dosimeter. The rate of thermal bleaching post-irradiation can be controlled by varying the ratios of the LMG to the radical activator and quantity of dissolution solvent. The ability to control the rate of losing the radiochromic dose distribution is an important characteristic for a potentially reusable dosimeter. Precautions must be taken to minimize the exposure of PRESAGE™ to room light. Research supported by Modus Medical and Heuris Pharma.

Isothermal and isochronal annealing experiments on irradiated commercial power VDMOSFETs

Describes effects in two types of gamma-ray irradiated power VDMOSFETs, commercially available from different manufacturers. Isothermal annealing with constant and switching gate bias, as well as isochronal annealing have been performed. The application of charge-pumping measurements in commercial three-terminal VDMOSFETs is also discussed. Besides enabling insight into the post-irradiation response of investigated devices, obtained results point out some interesting post-irradiation phenomena.

Radiation-induced interface traps in hardened MOS transistors: an improved charge-pumping study

Different electrical characterization (subthreshold current-voltage measurements, 3-level and multi-frequency charge pumping) combined with isochronal anneals have been used to investigate the generation and the evolution of interface traps in radiation-hardened MOS transistors following exposure to 10 keV X-rays. The evolution of the interface state density (D/sub it/) during the anneal is found to be field-dependent and consistent with models involving a drift of positive species towards the Si-SiO/sub 2/ interface. The energy-resolved distributions of D/sub it/ in the silicon bandgap show the emergence of two broad structures located at /spl sim/E/sub V/+0.35 eV and /spl sim/E/sub V/+0.75 eV immediately after irradiation and during the first steps of the isochronal anneal (up to /spl sim/175/spl deg/C). At higher anneal temperatures, it is shown that the recovery of D/sub it/ is not uniform in the two halves of the silicon bandgap. In particular, the separation of the D/sub it/ distribution related to the lower part of the bandgap in two distinct peaks (at E/sub V/+0.30 eV and E/sub V/+0.45 eV) agrees well with the energy distributions of P/sub b0/ and P/sub b1/ centers. These results are consistent with Electron Spin Resonance (ESR) studies which have shown that P/sub b/ centers play a dominating role in the interface trap build-up and recovery mechanisms. Since ESR measurements are only accurate to /spl sim//spl plusmn/30% in absolute number, P/sub b/ centers do not probably account for all the electrically active interface trap defects, as also suggested by the evident asymmetry of the D/sub it/ distributions in the bandgap. Finally, we investigate the post-irradiation response of border traps by reducing the charge pumping frequency to low values. The implication of these results on the nature of border traps is discussed.

Reversible positive charge annealing in MOS transistor during variety of electrical and thermal stresses

The postirradiation response of n-channel MOSTs during thermal and electrical stresses is investigated. It is found that reversible positive charge annealing plays a key role in the postirradiation response of the MOST. A mathematical model of reversible charge relaxation process is suggested.

Cell kinetics in rat small intestine after exposure to 3 Gy of gamma-rays at different times of the day.

Qualitative and quantitative morphological changes in rat jejunum were studied after a whole-body exposure to 3 Gy of gamma rays. Four groups of animals were irradiated at different times of the day, namely midnight, 06.00, 12.00 and 18.00 hours. The number of epithelial cells, labelling and mitotic indices were evaluated in crypt sections and the spatial distribution of S-phase cells was determined. At 12 h after irradiation a marked reduction was observed in all parameters, but the proliferative activity was restored quickly and at 36 h after irradiation the values were significantly higher than the controls. The frequency distribution of labelled cells at different positions in the crypt was reduced at 12 h but a clear expansion of S phase cells to positions near to the crypt villus junction was observed during the recovery phase. The animals irradiated at different times of the day showed a similar general post-irradiation response in the number of cells along the side of the crypt, labelling and mitotic indices and in the distribution of S phase cells along the crypts. It is worth noting that the animals exposed at midnight had a distribution of S phase cells similar to controls at 72 h post-irradiation, i.e. earlier than the other groups.

The role of border traps in MOS high-temperature postirradiation annealing response

A very-long-term study of the response of nonradiation-hardened MOS transistors to elevated-temperature, postirradiation biased anneals has been performed. The midgap-voltage shift of these devices returns to approximately 0 V during a 2.75-year, +6 V 100 degrees C anneal, supporting the idea that in these devices interface traps and border traps (near-interfacial oxide traps which can exchange charge with the underlying Si) are charge-neutral at midgap. Subsequent switched-bias annealing reveals that a significant fraction of the radiation-induced trapped holes have not been removed from the device, but are compensated by electrons in border traps. These border traps can lead to large, reversible changes in midgap-voltage shifts and/or subthreshold stretchout during switched-bias anneals. Midgap-voltage and subthreshold-stretchout reversibility remains significant in these devices even after annealing at temperatures up to 350 degrees C. Similar reversibility in postirradiation response is observed for hardened transistors and capacitors. These results suggest that border traps may lead to increased reliability problems in some irradiated devices as compared to their unirradiated counterparts.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Changes in Mineral Elements in Some Tissues of Mice Following Neutron Irradiation

Groups of mice were exposed to whole-body irradiation with moderately low fast neutron doses with 14 MeV average energy. The doses delivered to the internal soft tissues of mice were calculated. The changes in the concentrations of copper, magnesium, iron, zinc and calcium in the kidney, heart and spleen were estimated using atomic absorption spectrometry. Results revealed a significant reduction in the concentrations of these elements, 24 hours following irradiation with doses between 10 and 25 rem. Follow-up of the post-irradiation response was continued for 16 days for the 20 rem dose. A gradual increase in the concentration of the elements was noted which exceeded the pre-irradiation levels in most cases. However, by the end of the experiment, 16 days post-irradiation, some elements were still significantly below the control level.