Mark A. Tries

Monte Carlo characterization of an ytterbium‐169 high dose rate brachytherapy source with analysis of statistical uncertainty

An ytterbium-169 high dose rate brachytherapy source, distinguished by an intensity-weighted average photon energy of 92.7 keV and a 32.015 +/- 0.009 day half-life, is characterized in terms of the updated AAPM Task Group Report No. 43 specifications using the MCNP5 Monte Carlo computer code. In accordance with these specifications, the investigation included Monte Carlo simulations both in water and air with the in-air photon spectrum filtered to remove low-energy photons below 10 keV. TG-43 dosimetric data including S(K), D(r, lamda), lambda, gL(r), F(r, lamda), phi an(r), and phi(an) were calculated and statistical uncertainties in these parameters were derived and calculated in the appendix.

Novel Synthetic SOD/Catalase Mimetics Can Mitigate Capillary Endothelial Cell Apoptosis Caused by Ionizing Radiation

Abstract Numerous in vitro and in vivo studies have shown that the endothelial cells of the microvasculature of the lung and kidney are damaged by exposure to ionizing radiation, and this sustained endothelial cell injury is involved in the early and late radiation effects observed in these tissues. It is well accepted that ionizing radiation causes the generation of reactive oxygen species during exposure that results in damage to DNA and cellular organelles. It is more controversial, however, whether additional biochemical events or long-lived radicals occur and persist postirradiation that amplify and initiate new forms of cellular damage. Two families of Eukarion (EUK) compounds have been synthesized that possess superoxide dismutase (SOD), catalase and peroxidase activities. The Mn porphyrins are available orally whereas the salen Mn complexes are administered by injection. In the present study we have examined the ability of these SOD/catalase mimetics to prevent apoptosis of endothelial cells when administered 1 h postirradiation (mitigation). A range of salen Mn complex (EUK-189 and EUK-207) and Mn porphyrins (EUK-418, -423, -425, -450, -451, -452, -453) were used to treat endothelial cells 1 h after the cells received 2–20 Gy ionizing radiation in vitro. Two lead compounds, EUK-207 at a dose of 30 µM and EUK-451 at a dose of 10 µM, exhibited low toxicity and mitigated radiation-induced apoptosis. Future animal studies will test whether these compounds protect when administered after radiation exposure as would be done after a radiological accident or a terrorism event.

Retinoids and TIMP1 Prevent Radiation-Induced Apoptosis of Capillary Endothelial Cells

Abstract Vorotnikova, E., Tries, M. and Braunhut, S. J. Retinoids and TIMP1 Prevent Radiation-Induced Apoptosis of Capillary Endothelial Cells. Radiat. Res. 161, 174–184 (2004). Radiation-induced changes in capillaries constitute a basic injury in the pathogenesis of chronic radiation damage to the heart, lung, liver, kidney and brain. It is important to identify new radioprotectors for capillary endothelial cells for use during radiotherapy to minimize normal tissue damage and possibly to increase the deliverable dose. Previously we demonstrated that exposure to ionizing radiation (10 Gy) results in death of bovine adrenal capillary endothelial cells in confluent monolayers by apoptosis. We also showed that retinoids inhibit the growth of endothelial cells, induce their differentiation, down-regulate matrix metalloproteinase (MMP) production, and up-regulate tissue inhibitors of matrix metalloproteinases (TIMPs). In the present studies, we demonstrated that radiation (10 Gy) induced an immediate increase in the amounts and activation of MMP1 and MMP2 in the cell fraction and medium of bovine capillary endothelial cells followed by an incidence of apoptosis. We also obtained data indicating that radiation-induced apoptosis can be inhibited by exposing bovine capillary endothelial cells to all-trans-retinol or all-trans-retinoic acid for 6 days before irradiation, even when the vitamins were removed 24 h before irradiation. Finally, we determined that inhibition of MMPs by TIMP was sufficient to block radiation-induced apoptosis, suggesting that the mechanism of protection by retinoids is through the alteration of levels of MMPs and TIMPs produced by the cells.

The magnitude and time-dependence of the apoptotic response of normal and malignant cells subjected to ionizing radiation versus hyperthermia

Purpose: The purpose of the study was to examine the optimal time of exposure and dose of heat and ionizing radiation that results in the killing of human cancer cells in vitro via apoptosis vs. necrosis. Materials and methods: Human mammary carcinoma, colorectal carcinoma and normal bovine capillary endothelial (BCE) cell lines were subjected to 20 Gy ionizing radiation and 6, 12, 24, and 72 h later assessed for apoptosis using detection of apoptotic bodies and caspase assays. Necrosis was detected by loss of cells from the surface and lactate dehydrogenase (LDH) release. The colorectal carcinoma cells were subjected to hyperthermia using temperatures ranging from 39 – 44°C for 5, 15 or 45 min. exposures and at varying times post-treatment, apoptosis and necrosis were measured. Results: In response to ionizing radiation, none of the cells underwent necrosis and some cell types apoptosed 24 and 72 h posttreatment. The colorectal cancer cells exhibited a steady increase of apoptosis at 6, 12, and 24 h. When these cells were exposed to 40°C for 5 min, caspases increased within 6 h and a significant fraction (50%) of cells apoptosed. If the time of exposure to 40°C was increased to 15 or 45 min, 80% and 100% of the dying cells apoptosed, respectively. A temperature of 39°C did not cause cell death even after 45 min exposures. If heat was elevated to 42 or 44°C, increased necrosis was observed with a corresponding decrease in apoptosis. Conclusions: These studies reveal time and temperature dependent in vitro cell responses to ionizing radiation and water-bath hyperthermia.

Detection limits for samples that give rise to counting data with extra-Poisson variance.

Detection limits are presented for duplicate background samples that produced counting data with extra-Poisson variance that was attributed to a nonuniform activity distribution in the background sample medium. The presence of extra-Poisson variance was detected using the chi-squared test, where the presumed change in baseline activity from sample to sample was interpreted as an increase in experimental population variance. The runs test and Wilk-Shapiro test verified, respectively, the acceptable randomness of the data and the hypothesis that the data are normally distributed. Confidence intervals for detection limits therefore were based on the normal and t-distributions. The reduced chi-squared statistic was incorporated into the equations for the critical level and lower limit of detection to account for experimental variance beyond the expected Poisson value. The incorporation of extra-Poisson variance increased these detection limits for a well-defined background by a factor of 2.3 compared to the expected values for the paired-sample method which were derived under the assumption of Poisson variance, where the 30 background measurements have a reduced chi-squared statistic of 9.44.

National diagnostic reference level initiative for computed tomography examinations in Kenya

The purpose of this study was to estimate the computed tomography (CT) examination frequency, patient radiation exposure, effective doses and national diagnostic reference levels (NDRLs) associated with CT examinations in clinical practice. A structured questionnaire-type form was developed for recording examination frequency, scanning protocols and patient radiation exposure during CT procedures in fully equipped medical facilities across the country. The national annual number of CT examinations per 1000 people was estimated to be 3 procedures. The volume-weighted CT dose index, dose length product, effective dose and NDRLs were determined for 20 types of adult and paediatric CT examinations. Additionally, the CT annual collective effective dose and effective dose per capita were approximated. The radiation exposure during CT examinations was broadly distributed between the facilities that took part in the study. This calls for a need to develop and implement diagnostic reference levels as a standardisation and optimisation tool for the radiological protection of patients at all the CT facilities nationwide.

Patient radiation exposure during general fluoroscopy examinations

The purpose of this study was to assess the level of patient radiation dose received in general fluoroscopy examinations, compare the findings with the international diagnostic reference levels (IDRLs), and establish the initial institutional (local) LDRLs. A comprehensive survey was conducted for general fluoroscopy examinations using the medical records of a Radiology Department of a leading regional hospital over a period close to one year. The cumulative reference point air kerma (Ka,r), kerma area product (KAP) and fluoroscopy time (FT) were recorded for six hundred and fifty (30% pediatric and 70% adult) patients undergoing routine fluoroscopy examinations using X‐ray equipment with built‐in integrated dose measuring system. Results which were obtained for adult general fluoroscopy indicated that 83% and 33% were below the IDRLs for KAP and fluoroscopy time, respectively. In children, 60% were found to be below the only available KAP diagnostic reference levels. Local diagnostic reference levels (LDRLs) have been proposed with respect to the missing DRLs for the Ka r, KAP, and fluoroscopy time. The majority of the examinations in the study were performed with longer fluoroscopy time, patient dose values per examination type were found to be broad and the mean values above the international diagnostic reference levels. This calls for proper and improved training and radiation protection skills for the responsible personnel, especially the equipment operators. PACS numbers: 87.53.Bn, 87.59.C‐, 87.59.cf, 87.53.Bn, 87.50.‐a, 87.53.‐j

Applications of a quadratic variance model for counting data.

A quadratic variance model expressed as a function of sample mean is used to describe counting variance for a mechanical system that exhibits extra-Poisson variance. The nonlinear term describes the extra-Poisson variance, and the linear terms describe the intrinsic and propagated Poisson variance. The quadratic variance model also is applied to repetitive bioassay data, where the nonlinear term describes the well-known phenomenon of biological variance, which is a special case of extra-Poisson variance. The model was found to be suitable for the bioassay data as well. Detection limits for extra-Poisson variance are discussed, as well as the estimation of net signal detection limits, intake, and committed effective dose equivalent using the quadratic variance model.

Frequency and collective dose of medical procedures in Kenya.

AbstractThe first comprehensive national survey on frequency and radiation dose imparted to the population from radiological procedures was carried out in Kenya and reported here. This survey involved assessment of frequency, typical patient radiation exposure, and collective effective dose from general radiography, fluoroscopy, interventional procedures (IPs), mammography, and computed tomography. About 300 x-ray facilities across the country were invited to participate in the survey, and a 31% response was recorded. The individual and collective radiation burdens of more than 62 types of pediatric and adult radiological examinations were quantified using effective and collective dose. The average effective dose for each radiological examination was assessed from the x-ray efficiency performance tests and patient data from over 30 representative radiological facilities. The results found indicated that over 3 million x-ray procedures were performed in 2011, resulting in an annual collective effective dose of 2,157 person-Sv and an annual effective dose per capita of 0.05 mSv. The most frequent examinations were general radiography (94%), computed tomography (3.3%), and fluoroscopy (2.5%). Although the contribution of computed tomography was small in terms of frequency, this procedure accounted for 36% of the effective dose per capita. General radiography was the most frequent type of examination with a contribution of 55% of the effective dose per capita.

Basic applications of the chi-square statistic using counting data.

The chi-square statistic has many scientific applications, including the evaluation of variance in counting data and the proper functioning of a radiation counting system. This paper provides a discussion of the fundamental aspects of the chi-square test using counting data. Practical applications of the chi-square statistic are discussed, including the estimation of extra-Poisson variance and dead time for a counting system. The consequences of passing or failing the chi-square test are discussed regarding the proper estimator for the population variance of the counting data. Example scenarios are used to provide insight into the applications of the chi-square statistic and the interpretation of values obtained in hypothesis testing.