Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

PubMed

Duong, Phuong-Anh; Little, Brent P

2014-08-01

Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

Digital radiography: optimization of image quality and dose using multi-frequency software.

PubMed

Precht, H; Gerke, O; Rosendahl, K; Tingberg, A; Waaler, D

2012-09-01

New developments in processing of digital radiographs (DR), including multi-frequency processing (MFP), allow optimization of image quality and radiation dose. This is particularly promising in children as they are believed to be more sensitive to ionizing radiation than adults. To examine whether the use of MFP software reduces the radiation dose without compromising quality at DR of the femur in 5-year-old-equivalent anthropomorphic and technical phantoms. A total of 110 images of an anthropomorphic phantom were imaged on a DR system (Canon DR with CXDI-50 C detector and MLT[S] software) and analyzed by three pediatric radiologists using Visual Grading Analysis. In addition, 3,500 images taken of a technical contrast-detail phantom (CDRAD 2.0) provide an objective image-quality assessment. Optimal image-quality was maintained at a dose reduction of 61% with MLT(S) optimized images. Even for images of diagnostic quality, MLT(S) provided a dose reduction of 88% as compared to the reference image. Software impact on image quality was found significant for dose (mAs), dynamic range dark region and frequency band. By optimizing image processing parameters, a significant dose reduction is possible without significant loss of image quality.

A study on the indirect urea dosing method in the Selective Catalytic Reduction system

NASA Astrophysics Data System (ADS)

Brzeżański, M.; Sala, R.

2016-09-01

This article presents the results of studies on concept solution of dosing urea in a gas phase in a selective catalytic reduction system. The idea of the concept was to heat-up and evaporate the water urea solution before introducing it into the exhaust gas stream. The aim was to enhance the processes of urea converting into ammonia, what is the target reductant for nitrogen oxides treatment. The study was conducted on a medium-duty Euro 5 diesel engine with exhaust line consisting of DOC catalyst, DPF filter and an SCR system with a changeable setup allowing to dose the urea in liquid phase (regular solution) and to dose it in a gas phase (concept solution). The main criteria was to assess the effect of physical state of urea dosed on the NOx conversion ratio in the SCR catalyst. In order to compare both urea dosing methods a special test procedure was developed which consisted of six test steps covering a wide temperature range of exhaust gas generated at steady state engine operation condition. Tests were conducted for different urea dosing quantities defined by the a equivalence ratio. Based on the obtained results, a remarkable improvement in NOx reduction was found for gas urea application in comparison to the standard liquid urea dosing. Measured results indicate a high potential to increase an efficiency of the SCR catalyst by using a gas phase urea and provide the basis for further scientific research on this type of concept.

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

Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

PubMed

Shao, Kan; Small, Mitchell J

2011-10-01

A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

PubMed

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

2013-12-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. Copyright © 2013 Elsevier Inc. All rights reserved.

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT

PubMed Central

Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg

2012-01-01

Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512

Monte Carlo simulations to assess the effects of tube current modulation on breast dose for multidetector CT

NASA Astrophysics Data System (ADS)

Angel, Erin; Yaghmai, Nazanin; Matilda Jude, Cecilia; DeMarco, John J.; Cagnon, Christopher H.; Goldin, Jonathan G.; Primak, Andrew N.; Stevens, Donna M.; Cody, Dianna D.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

2009-02-01

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient's glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient's clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.

Measles control in developing and developed countries: the case for a two-dose policy.

PubMed

Tulchinsky, T H; Ginsberg, G M; Abed, Y; Angeles, M T; Akukwe, C; Bonn, J

1993-01-01

Despite major reductions in the incidence of measles and its complications, measles control with a single dose of the currently used. Schwarz strain vaccine has failed to eradicate the disease in the developed countries. In developing countries an enormous toll of measles deaths and disability continues, despite considerable efforts and increasing immunization coverage. Empirical evidence from a number of countries suggests that a two-dose measles vaccination programme, by improving individual protection and heard immunity can make a major contribution to measles control and elimination of local circulation of the disease. Cost-benefit analysis also supports the two-dose schedule in terms of savings in health costs, and total costs to society. A two-dose measles vaccination programme is therefore an essential component of preventive health care in developing, as well as developed countries for the 1990s.

[Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

PubMed

Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

2015-07-01

The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Dose reduction potential of iterative reconstruction algorithms in neck CTA-a simulation study.

PubMed

Ellmann, Stephan; Kammerer, Ferdinand; Allmendinger, Thomas; Brand, Michael; Janka, Rolf; Hammon, Matthias; Lell, Michael M; Uder, Michael; Kramer, Manuel

2016-10-01

This study aimed to determine the degree of radiation dose reduction in neck CT angiography (CTA) achievable with Sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 10 consecutive patients scheduled for neck CTA were included in this study. CTA images of the external carotid arteries either were reconstructed with filtered back projection (FBP) at full radiation dose level or underwent simulated dose reduction by proprietary reconstruction software. The dose-reduced images were reconstructed using either SAFIRE 3 or SAFIRE 5 and compared with full-dose FBP images in terms of vessel definition. 5 observers performed a total of 3000 pairwise comparisons. SAFIRE allowed substantial radiation dose reductions in neck CTA while maintaining vessel definition. The possible levels of radiation dose reduction ranged from approximately 34 to approximately 90% and depended on the SAFIRE algorithm strength and the size of the vessel of interest. In general, larger vessels permitted higher degrees of radiation dose reduction, especially with higher SAFIRE strength levels. With small vessels, the superiority of SAFIRE 5 over SAFIRE 3 was lost. Neck CTA can be performed with substantially less radiation dose when SAFIRE is applied. The exact degree of radiation dose reduction should be adapted to the clinical question, in particular to the smallest vessel needing excellent definition.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

PubMed Central

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

2013-01-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. PMID:24201048

A study on the dependence of exposure dose reduction and image evaluation on the distance from the dental periapical X-ray machine

NASA Astrophysics Data System (ADS)

Joo, Kyu-Ji; Shin, Jae-Woo; Dong, Kyung-Rae; Lim, Chang-Seon; Chung, Woon-Kwan; Kim, Young-Jae

2013-11-01

Reducing the exposure dose from a periapical X-ray machine is an important aim in dental radiography. Although the radiation exposure dose is generally low, any radiation exposure is harmful to the human body. Therefore, this study developed a method that reduces the exposure dose significantly compared to that encountered in a normal procedure, but still produces an image with a similar resolution. The correlation between the image resolution and the exposure dose of the proposed method was examined with increasing distance between the dosimeter and the X-ray tube. The results were compared with those obtained from the existing radiography method. When periapical radiography was performed once according to the recommendations of the International Commission on Radiological Protection (ICRP), the measured skin surface dose was low at 7 mGy or below. In contrast, the skin surface dose measured using the proposed method was only 1.57 mGy, showing a five-fold reduction. These results suggest that further decreases in dose might be achieved using the proposed method.

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

PubMed

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol

PubMed Central

Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.

2009-01-01

The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p < 0.05) reductions in penile length, weight, and diameter. Additionally, the penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

125I eye plaque dose distribution including penumbra characteristics.

PubMed

de la Zerda, A; Chiu-Tsao, S T; Lin, J; Boulay, L L; Kanna, I; Kim, J H; Tsao, H S

1996-03-01

The two main purposes of this work are (1) to determine the penumbra characteristics for 125I eye plaque and the relative influence of the plaque and eye-air interface on the dose distribution, and (2) to initiate development of a treatment planning algorithm for clinical dose calculations. Dose was measured in a newly designed solid water eye phantom for an 125I (6711) seed at the center of a 20 mm COMS eye plaque using thermoluminescent dosimeter (TLD) "cubes" and "minichips" inside and outside the eye, in the longitudinal and transverse central planes. TLD cubes were used in most locations, except for short distances from the seed and in the penumbra region. In the presence of both the plaque and the eye-air interface, the dose along the central axis was found to be reduced by 10% at 1 cm and up to 20% at 2.5 cm, relative to the bulk homogeneous phantom case. In addition, the overall dose reduction was greater for larger off-axis coordinates at a given depth. The penumbra characteristics due to the lip collimation were quantified, particularly the dependence of penumbra center and width on depth. Only small differences were observed between the profiles in the transverse and longitudinal planes. In the bulk geometry (without the eye-air interface), the dose reduction due to the presence of the plaque alone was found to be 7% at a depth of 2.5 cm. The additional reduction of 13% observed, with the presence of eye-air interface (20% combined), can be attributed to the lack of backscattering from the air in front of the eye. The dose-reduction effect due to the anterior air interface alone became unnoticeable at a depth of 1.1 cm (1.5 cm from the eye-air interface). An analytic fit to measured data was developed for clinical dose calculations for a centrally loaded seed. The central axis values of the dose rates multiplied by distance squared, Dr2, were fitted with a double exponential function of depth. The off-axis profile of Dr2, at a given depth, was parametrized by a modified Fermi-Dirac function to model both the penumbra characteristics due the plaque lip collimation and the effect of oblique filtration by silastic.

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach

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

Sasso, A.F., E-mail: sasso.alan@epa.gov; Schlosser, P.M., E-mail: schlosser.paul@epa.gov

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastricmore » juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. - Highlights: • We outline a new in vivo model for hexavalent chromium reduction in the stomach. • We examine in vivo reduction for mice, rats, and humans under varying conditions. • Species differences in toxicokinetics may explain susceptibility. • We show that a simplified stomach reduction model is adequate for extrapolation. • Internal dose uncertainties still exist.« less

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia.

PubMed

Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu

2014-07-01

Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters.

PubMed

Sun, Wenzhao; Wang, Bin; Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-03-21

To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

The anthelmintic effect of aqueous methanol extract of Combretum molle (R. Br. x. G. Don) (Combretaceae) in lambs experimentally infected with Haemonchus contortus.

PubMed

Simon, M K; Ajanusi, O J; Abubakar, M S; Idris, A L; Suleiman, M M

2012-06-08

The aqueous methanol extract from the stem-bark of Combretum molle was evaluated for anthelmintic activity in lambs infected with Haemonchus contortus using faecal egg count (FEC) reduction assay. The extract showed a dose-dependent reduction in FEC in infected animals. At doses of 500, 1000 and 2000 mg kg(-1), the extract caused FEC reduction of 63%, 69.25% and 96.23%, respectively. Similarly, the standard anthelmintic (albendazole) at a dose of 200 mg kg(-1) produced FEC reduction of 99.24%. FEC reduction produced by the extract at doses of 500 and 1000 mg kg(-1) is below the minimum standard of 90% FEC recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP). However, there was no significant (P>0.05) difference between the means of groups treated with 1000 mg kg(-1) and 2000 mg kg(-1) compared to that of albendazole. In this study, C. molle has shown a promising anthelmintic activity against experimental haemonchosis. Nonetheless, further studies to evaluate its detailed toxicity are required for the plant extract to be developed into a useful anthelmintic drug. There is also the need to evaluate other parts of the plant (root, leaves, fruits, etc.) for the same effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes.

PubMed

Colombo, John; Jill Shaddy, D; Kerling, Elizabeth H; Gustafson, Kathleen M; Carlson, Susan E

2017-06-01

The DHA Intake and Measurement of Neural Development (DIAMOND) trial represents one of only a few studies of the long-term dose-response effects of LCPUFA-supplemented formula feeding during infancy. The trial contrasted the effects of four formulations: 0.00% docosahexaenoic acid (DHA)/0.00% arachidonic acid (ARA), 0.32% DHA/0.64% ARA, 0.64% DHA/0.64% ARA, and 0.96% DHA/0.64% ARA against a control condition (0.00% DHA/0.00% ARA). The results of this trial have been published elsewhere, and show improved cognitive outcomes for infants fed supplemented formulas, but a common finding among many of the outcomes show a reduction of benefit for the highest DHA dose (i.e., 0.96%DHA/0.64% ARA, that is, a DHA: ARA ratio 1.5:1.0). The current paper gathers and summarizes the evidence for the reduction of benefit at this dose, and in an attempt to account for this reduced benefit, presents for the first time data from infants' red blood cell (RBC) assays taken at 4 and 12 months of age. Those assays indicate that blood DHA levels generally rose with increased DHA supplementation, although those levels tended to plateau as the DHA-supplemented level exceeded 0.64%. Perhaps more importantly, ARA levels showed a strong inverted-U function in response to increased DHA supplementation; indeed, infants assigned to the formula with the highest dose of DHA (and highest DHA/ARA ratio) showed a reduction in blood ARA relative to more intermediate DHA doses. This finding raises the possibility that reduced ARA may be responsible for the reduction in benefit on cognitive outcomes seen at this dose. The findings implicate the DHA/ARA balance as an important variable in the contribution of LCPUFAs to cognitive and behavioral development in infancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

EVALUATION OF CHITOSAN COAGULATION AS A SUSTAINABLE METHOD FOR POINT OF USE DRINKINGWATER TREATMENT IN DEVELOPING COUNTRIES

EPA Science Inventory

Chitosan A was found to remove up to 3.4 log₁₀ E. coli, a reduction of 99.96%. The removal was dose dependent; up to a point, removal of E. coli increases with increasing dose. Removal of E. coli ranged from 0% removal by a dose of 1g/L to...

First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy.

PubMed

Silber, J H; Fridman, M; DiPaola, R S; Erder, M H; Pauly, M V; Fox, K R

1998-07-01

If patients could be ranked according to their projected need for supportive care therapy, then more efficient and less costly treatment algorithms might be developed. This work reports on the construction of a model of neutropenia, dose reduction, or delay that rank-orders patients according to their need for costly supportive care such as granulocyte growth factors. A case series and consecutive sample of patients treated for breast cancer were studied. Patients had received standard-dose adjuvant chemotherapy for early-stage nonmetastatic breast cancer and were treated by four medical oncologists. Using 95 patients and validated with 80 additional patients, development models were constructed to predict one or more of the following events: neutropenia (absolute neutrophil count [ANC] < or = 250/microL), dose reduction > or = 15% of that scheduled, or treatment delay > or = 7 days. Two approaches to modeling were attempted. The pretreatment approach used only pretreatment predictors such as chemotherapy regimen and radiation history; the conditional approach included, in addition, blood count information obtained in the first cycle of treatment. The pretreatment model was unsuccessful at predicting neutropenia, dose reduction, or delay (c-statistic = 0.63). Conditional models were good predictors of subsequent events after cycle 1 (c-statistic = 0.87 and 0.78 for development and validation samples, respectively). The depth of the first-cycle ANC was an excellent predictor of events in subsequent cycles (P = .0001 to .004). Chemotherapy plus radiation also increased the risk of subsequent events (P = .0011 to .0901). Decline in hemoglobin (HGB) level during the first cycle of therapy was a significant predictor of events in the development study (P = .0074 and .0015), and although the trend was similar in the validation study, HGB decline failed to reach statistical significance. It is possible to rank patients according to their need of supportive care based on blood counts observed in the first cycle of therapy. Such rankings may aid in the choice of appropriate supportive care for patients with early-stage breast cancer.

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach.

PubMed

Sasso, A F; Schlosser, P M

2015-09-15

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. Published by Elsevier Inc.

Effect of reduced agalsidase Beta dosage in fabry patients: the Australian experience.

PubMed

Ghali, Joanna; Nicholls, Kathy; Denaro, Charles; Sillence, David; Chapman, Ian; Goldblatt, Jack; Thomas, Mark; Fletcher, Janice

2012-01-01

In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009. To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort. A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction. Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa. This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.

Efficacy of radiation safety glasses in interventional radiology.

PubMed

van Rooijen, Bart D; de Haan, Michiel W; Das, Marco; Arnoldussen, Carsten W K P; de Graaf, R; van Zwam, Wim H; Backes, Walter H; Jeukens, Cécile R L P N

2014-10-01

This study was designed to evaluate the reduction of the eye lens dose when wearing protective eyewear in interventional radiology and to identify conditions that optimize the efficacy of radiation safety glasses. The dose reduction provided by different models of radiation safety glasses was measured on an anthropomorphic phantom head. The influence of the orientation of the phantom head on the dose reduction was studied in detail. The dose reduction in interventional radiological practice was assessed by dose measurements on radiologists wearing either leaded or no glasses or using a ceiling suspended screen. The different models of radiation safety glasses provided a dose reduction in the range of a factor of 7.9-10.0 for frontal exposure of the phantom. The dose reduction was strongly reduced when the head is turned to the side relative to the irradiated volume. The eye closest to the tube was better protected due to side shielding and eyewear curvature. In clinical practice, the mean dose reduction was a factor of 2.1. Using a ceiling suspended lead glass shield resulted in a mean dose reduction of a factor of 5.7. The efficacy of radiation protection glasses depends on the orientation of the operator's head relative to the irradiated volume. Glasses can offer good protection to the eye under clinically relevant conditions. However, the performance in clinical practice in our study was lower than expected. This is likely related to nonoptimized room geometry and training of the staff as well as measurement methodology.

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters

PubMed Central

Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-01-01

Objective: To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Materials and Methods: Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. Results: The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Conclusions: Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification. PMID:28423624

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

PubMed Central

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

2015-01-01

Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PubMed

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

2015-08-01

Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

Radiation dose reduction efficiency of buildings after the accident at the Fukushima Daiichi Nuclear Power Station.

PubMed

Monzen, Satoru; Hosoda, Masahiro; Osanai, Minoru; Tokonami, Shinji

2014-01-01

Numerous radionuclides were released from the Fukushima Daiichi Nuclear Power Station (F1-NPS) in Japan following the magnitude 9.0 earthquake and tsunami on March 11, 2011. Local residents have been eager to calculate their individual radiation exposure. Thus, absorbed dose rates in the indoor and outdoor air at evacuation sites in the Fukushima Prefecture were measured using a gamma-ray measuring devices, and individual radiation exposure was calculated by assessing the radiation dose reduction efficiency (defined as the ratio of absorbed dose rate in the indoor air to the absorbed dose rate in the outdoor air) of wood, aluminum, and reinforced concrete buildings. Between March 2011 and July 2011, dose reduction efficiencies of wood, aluminum, and reinforced concrete buildings were 0.55 ± 0.04, 0.15 ± 0.02, and 0.19 ± 0.04, respectively. The reduction efficiency of wood structures was 1.4 times higher than that reported by the International Atomic Energy Agency. The efficiency of reinforced concrete was similar to previously reported values, whereas that of aluminum structures has not been previously reported. Dose reduction efficiency increased in proportion to the distance from F1-NPS at 8 of the 18 evacuation sites. Time variations did not reflect dose reduction efficiencies at evacuation sites although absorbed dose rates in the outdoor air decreased. These data suggest that dose reduction efficiency depends on structure types, levels of contamination, and evacuee behaviors at evacuation sites.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom

PubMed Central

Goren, AD; Prins, RD; Dauer, LT; Quinn, B; Al-Najjar, A; Faber, RD; Patchell, G; Branets, I; Colosi, DC

2013-01-01

Objectives: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. Methods: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. Results: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). Conclusions: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view. PMID:23412460

A new shielding calculation method for X-ray computed tomography regarding scattered radiation.

PubMed

Watanabe, Hiroshi; Noto, Kimiya; Shohji, Tomokazu; Ogawa, Yasuyoshi; Fujibuchi, Toshioh; Yamaguchi, Ichiro; Hiraki, Hitoshi; Kida, Tetsuo; Sasanuma, Kazutoshi; Katsunuma, Yasushi; Nakano, Takurou; Horitsugi, Genki; Hosono, Makoto

2017-06-01

The goal of this study is to develop a more appropriate shielding calculation method for computed tomography (CT) in comparison with the Japanese conventional (JC) method and the National Council on Radiation Protection and Measurements (NCRP)-dose length product (DLP) method. Scattered dose distributions were measured in a CT room with 18 scanners (16 scanners in the case of the JC method) for one week during routine clinical use. The radiation doses were calculated for the same period using the JC and NCRP-DLP methods. The mean (NCRP-DLP-calculated dose)/(measured dose) ratios in each direction ranged from 1.7 ± 0.6 to 55 ± 24 (mean ± standard deviation). The NCRP-DLP method underestimated the dose at 3.4% in fewer shielding directions without the gantry and a subject, and the minimum (NCRP-DLP-calculated dose)/(measured dose) ratio was 0.6. The reduction factors were 0.036 ± 0.014 and 0.24 ± 0.061 for the gantry and couch directions, respectively. The (JC-calculated dose)/(measured dose) ratios ranged from 11 ± 8.7 to 404 ± 340. The air kerma scatter factor κ is expected to be twice as high as that calculated with the NCRP-DLP method and the reduction factors are expected to be 0.1 and 0.4 for the gantry and couch directions, respectively. We, therefore, propose a more appropriate method, the Japanese-DLP method, which resolves the issues of possible underestimation of the scattered radiation and overestimation of the reduction factors in the gantry and couch directions.

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT.

PubMed

Chatterson, Leslie C; Leswick, David A; Fladeland, Derek A; Hunt, Megan M; Webster, Stephen; Lim, Hyun

2014-07-01

Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P<0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P<0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P=0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P=0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal organ dose during CTPA. Shields continue to be an effective means of fetal dose reduction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Morrow, David A; Murphy, Sabina A; Kuder, Julia F; Deenadayalu, Naveen; Jarolim, Petr; Betcher, Joshua; Shi, Minggao; Brown, Karen; Patel, Indravadan; Mercuri, Michele; Antman, Elliott M

2015-06-06

New oral anticoagulants for stroke prevention in atrial fibrillation were developed to be given in fixed doses without the need for the routine monitoring that has hindered usage and acceptance of vitamin K antagonists. A concern has emerged, however, that measurement of drug concentration or anticoagulant activity might be needed to prevent excess drug concentrations, which significantly increase bleeding risk. In the ENGAGE AF-TIMI 48 trial, higher-dose and lower-dose edoxaban were compared with warfarin in patients with atrial fibrillation. Each regimen incorporated a 50% dose reduction in patients with clinical features known to increase edoxaban drug exposure. We aim to assess whether adjustment of edoxaban dose in this trial prevented excess drug concentration and the risk of bleeding events. We analysed data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. We correlated edoxaban dose, plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and safety outcomes with warfarin stratified by dose reduction status. Patients with atrial fibrillation and at moderate to high risk of stroke were randomly assigned in a 1:1:1 ratio to receive warfarin, dose adjusted to an international normalised ratio of 2·0-3·0, higher-dose edoxaban (60 mg once daily), or lower-dose edoxaban (30 mg once daily). Randomisation was done with use of a central, 24 h, interactive, computerised response system. International normalised ratio was measured using an encrypted point-of-care device. To maintain masking, sham international normalised ratio values were generated for patients assigned to edoxaban. Edoxaban (or placebo-edoxaban in warfarin group) doses were halved at randomisation or during the trial if patients had creatinine clearance 30-50 mL/min, bodyweight 60 kg or less, or concomitant medication with potent P-glycoprotein interaction. Efficacy outcomes included the primary endpoint of all-cause stroke or systemic embolism, ischaemic stroke, and all-cause mortality. Safety outcomes included the primary safety endpoint of major bleeding, fatal bleeding, intracranial haemorrhage, and gastrointestinal bleeding. This trial is registered with ClinicalTrials.gov, number NCT00781391. Between Nov 19, 2008 and Nov 22, 2010, 21 105 patients were recruited. Patients who met clinical criteria for dose reduction at randomisation (n=5356) had higher rates of stroke, bleeding, and death compared with those who did not have a dose reduction (n=15 749). Edoxaban dose ranged from 15 mg to 60 mg, resulting in a two-fold to three fold gradient of mean trough drug exposure (16·0-48·5 ng/mL in 6780 patients with data available) and mean trough anti-FXa activity (0·35-0·85 IU/mL in 2865 patients). Dose reduction decreased mean exposure by 29% (from 48·5 ng/mL [SD 45·8] to 34·6 ng/mL [30·9]) and 35% (from 24·5 ng/mL [22·7] to 16·0 ng/mL [14·5]) and mean anti-FXa activity by 25% (from 0·85 IU/mL [0·76] to 0·64 IU/mL [0·54]) and 20% (from 0·44 IU/mL [0·37] to 0·35 IU/mL [0·28]) in the higher-dose and lower-dose regimens, respectively. Despite the lower anti-FXa activity, dose reduction preserved the efficacy of edoxaban compared with warfarin (stroke or systemic embolic event: higher dose pinteraction=0·85, lower dose pinteraction=0·99) and provided even greater safety (major bleeding: higher dose pinteraction 0·02, lower dose pinteraction=0·002). These findings validate the strategy that tailoring of the dose of edoxaban on the basis of clinical factors alone achieves the dual goal of preventing excess drug concentrations and helps to optimise an individual patient's risk of ischaemic and bleeding events and show that the therapeutic window for edoxaban is narrower for major bleeding than thromboembolism. Daiichi-Sankyo Pharma Development. Copyright © 2015 Elsevier Ltd. All rights reserved.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

NASA Astrophysics Data System (ADS)

Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

2017-04-01

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

Standard Pentostatin Dose Reductions in Renal Insufficiency are not Adequate: Selected Patients with Steroid-Refractory Acute Graft-versus-Host Disease

PubMed Central

Poi, Ming J.; Hofmeister, Craig C.; Johnston, Jeffrey S.; Edwards, Ryan B.; Jansak, Buffy S.; Lucas, David M.; Farag, Sherif S.; Dalton, James T.; Devine, Steven M.; Grever, Michael R.; Phelps, Mitch A.

2013-01-01

Background and Objective Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose reduction equations for patients with renal insufficiency are based on few patients with limited pharmacokinetic and clinical results. This phase II study (NCT00201786) was conducted to assess pentostatin efficacy and infectious complications seen from our previous phase I study in steroid-refractory acute GVHD (aGVHD). Patients and Methods Hospitalized patients with steroid-refractory aGVHD were given pentostatin 1.5 mg/m2/day intravenously on days 1–3 of each 14 day cycle. Prior to each dose, dose modifications were based on Cockcroft-Gault estimated creatinine clearance (eCrCL) with 30–50 ml/min/1.73m2 leading to a 50% dose reduction and eCrCL< 30 ml/min/1.73m2 leading to study removal. Plasma pentostatin area under the concentration-time curve (AUC) and incidence of infectious complications were evaluated. Results Two of the eight patients treated demonstrated excessive pentostatin exposure as determined by measurement of AUC. One of these patients had renal impairment while the other patient demonstrated borderline renal function. Despite dose reduction to 0.75 mg/m2, AUCs were significantly increased compared to the other patients in this study. Seven of eight patients treated with pentostatin had cytomegalovirus (CMV) viremia after pentostatin treatment; however none developed proven CMV disease. Conclusion A 50% dose reduction in patients with eCrCL 30–50 ml/min/1.73m2 seems reasonable. However, the eCrCL should be interpreted with extreme cautions in patients who are critically ill and/or with poor performance status. Renal function assessment based on the Cockcroft-Gault method could be significantly overestimated thus risking pentostatin over-dosing. These results imply a need to closely monitor pentostatin exposure in patients with renal insufficiency. PMID:23588536

Does Iterative Reconstruction Lower CT Radiation Dose: Evaluation of 15,000 Examinations

PubMed Central

Noël, Peter B.; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A.; Rummeny, Ernst J.; Dobritz, Martin

2013-01-01

Purpose Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Method and Materials Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. Results IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). Conclusion The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving. PMID:24303035

Does iterative reconstruction lower CT radiation dose: evaluation of 15,000 examinations.

PubMed

Noël, Peter B; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A; Rummeny, Ernst J; Dobritz, Martin

2013-01-01

Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving.

Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats

EPA Science Inventory

Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...

Use of a channelized Hotelling observer to assess CT image quality and optimize dose reduction for iteratively reconstructed images.

PubMed

Favazza, Christopher P; Ferrero, Andrea; Yu, Lifeng; Leng, Shuai; McMillan, Kyle L; McCollough, Cynthia H

2017-07-01

The use of iterative reconstruction (IR) algorithms in CT generally decreases image noise and enables dose reduction. However, the amount of dose reduction possible using IR without sacrificing diagnostic performance is difficult to assess with conventional image quality metrics. Through this investigation, achievable dose reduction using a commercially available IR algorithm without loss of low contrast spatial resolution was determined with a channelized Hotelling observer (CHO) model and used to optimize a clinical abdomen/pelvis exam protocol. A phantom containing 21 low contrast disks-three different contrast levels and seven different diameters-was imaged at different dose levels. Images were created with filtered backprojection (FBP) and IR. The CHO was tasked with detecting the low contrast disks. CHO performance indicated dose could be reduced by 22% to 25% without compromising low contrast detectability (as compared to full-dose FBP images) whereas 50% or more dose reduction significantly reduced detection performance. Importantly, default settings for the scanner and protocol investigated reduced dose by upward of 75%. Subsequently, CHO-based protocol changes to the default protocol yielded images of higher quality and doses more consistent with values from a larger, dose-optimized scanner fleet. CHO assessment provided objective data to successfully optimize a clinical CT acquisition protocol.

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction

PubMed Central

Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-01-01

Introduction Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. Materials and Methods A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Results Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13–53.8% reduction in low dose protocol. Conclusion The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose. PMID:27437322

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction.

PubMed

Koteshwar, Prakashini; Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-05-01

Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13-53.8% reduction in low dose protocol. The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose.

Can image enhancement allow radiation dose to be reduced whilst maintaining the perceived diagnostic image quality required for coronary angiography?

PubMed Central

Joshi, Anuja; Gislason-Lee, Amber J; Keeble, Claire; Sivananthan, Uduvil M

2017-01-01

Objective: The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Methods: Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10–89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states—with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. Results: Observers rated the quality of the images processed with the state-of-the-art and previous generation image processing with a 24.9% and 15.6% dose reduction, respectively, as equivalent in quality to the unenhanced images. The dose reduction facilitated by the state-of-the-art image processing relative to previous generation processing was 10.3%. Conclusion: Results demonstrate that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. Advances in knowledge: Image enhancement was shown to maintain perceived image quality in coronary angiography at a reduced level of radiation dose using computer software to produce synthetic images from real angiograms simulating a reduction in dose. PMID:28124572

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

PubMed

Barrett, A; Depledge, M H; Powles, R L

1983-07-01

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

Dose and risk in diagnostic radiology: How big How little Lecture Number 16

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

Webster, E.W.

1992-01-01

This lecture is divided into two parts: dose and risk. The dose segment is technical and noncontroversial since it deals with straightforward measurements or calculations which do not depend on unproven hypotheses. Some conflicting contributions of low dose epidemiological studies to the appraisal of risk are briefly presented. Attention is focused on the following: dose reduction in radiography; dose reduction in fluoroscopy; limitations of dose reduction; estimated radiation risks for diagnostic radiology examinations; excess breast cancer following X-ray examinations for scoliosis; dose-response relation for human mammary cancer; lung cancer from protracted X-irradiation; leukemia and diagnostic X-ray exposure; and thyroid cancermore » after diagnostic dose of I-131.« less

Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial.

PubMed

van Herwaarden, Noortje; van der Maas, Aatke; Minten, Michiel J M; van den Hoogen, Frank H J; Kievit, Wietske; van Vollenhoven, Ronald F; Bijlsma, Johannes W J; van den Bemt, Bart J F; den Broeder, Alfons A

2015-04-09

To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Randomised controlled, open label, non-inferiority strategy trial. Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events. Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval -12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.Trial registration Dutch trial register (www.trialregister.nl), NTR 3216. © van Herwaarden et al 2015.

A dose ranging study of ibuprofen suspension as an antipyretic.

PubMed Central

Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A

1991-01-01

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

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

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study.

PubMed

Raghuram, Kamini; Dunn, Michael; Jangaard, Krista; Reilly, Maureen; Asztalos, Elizabeth; Kelly, Edmond; Vincer, Michael; Shah, Vibhuti

2018-05-07

Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 μg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO 2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO 2 at a dose of 800 μg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 μg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .

Edge enhancement algorithm for low-dose X-ray fluoroscopic imaging.

PubMed

Lee, Min Seok; Park, Chul Hee; Kang, Moon Gi

2017-12-01

Low-dose X-ray fluoroscopy has continually evolved to reduce radiation risk to patients during clinical diagnosis and surgery. However, the reduction in dose exposure causes quality degradation of the acquired images. In general, an X-ray device has a time-average pre-processor to remove the generated quantum noise. However, this pre-processor causes blurring and artifacts within the moving edge regions, and noise remains in the image. During high-pass filtering (HPF) to enhance edge detail, this noise in the image is amplified. In this study, a 2D edge enhancement algorithm comprising region adaptive HPF with the transient improvement (TI) method, as well as artifacts and noise reduction (ANR), was developed for degraded X-ray fluoroscopic images. The proposed method was applied in a static scene pre-processed by a low-dose X-ray fluoroscopy device. First, the sharpness of the X-ray image was improved using region adaptive HPF with the TI method, which facilitates sharpening of edge details without overshoot problems. Then, an ANR filter that uses an edge directional kernel was developed to remove the artifacts and noise that can occur during sharpening, while preserving edge details. The quantitative and qualitative results obtained by applying the developed method to low-dose X-ray fluoroscopic images and visually and numerically comparing the final images with images improved using conventional edge enhancement techniques indicate that the proposed method outperforms existing edge enhancement methods in terms of objective criteria and subjective visual perception of the actual X-ray fluoroscopic image. The developed edge enhancement algorithm performed well when applied to actual low-dose X-ray fluoroscopic images, not only by improving the sharpness, but also by removing artifacts and noise, including overshoot. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety and dose modification for patients receiving niraparib.

PubMed

Berek, J S; Matulonis, U A; Peen, U; Ghatage, P; Mahner, S; Redondo, A; Lesoin, A; Colombo, N; Vergote, I; Rosengarten, O; Ledermann, J; Pineda, M; Ellard, S; Sehouli, J; Gonzalez-Martin, A; Berton-Rigaud, D; Madry, R; Reinthaller, A; Hazard, S; Guo, W; Mirza, M R

2018-05-14

Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions. All analyses were performed on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (ie, as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cutoff points for chosen variables. Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL in effect received an average daily dose approximating 200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 mg or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. The analysis presented suggests that patients with baseline body weight of < 77 kg or baseline platelets of < 150,000/μL may benefit from a starting dose of 200 mg per day. (ClinicalTrials.gov ID: NCT01847274).

Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

PubMed

Powers, Anna; Loesch, Erin B; Weiland, Anthony; Fioravanti, Nicole; Lucius, David

2017-07-01

To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard of practice.

Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation.

PubMed

Yeung, Rosanna; Conroy, Leigh; Long, Karen; Walrath, Daphne; Li, Haocheng; Smith, Wendy; Hudson, Alana; Phan, Tien

2015-09-22

Deep inspiration breath hold (DIBH) reduces heart and left anterior descending artery (LAD) dose during left-sided breast radiation therapy (RT); however there is limited information about which patients derive the most benefit from DIBH. The primary objective of this study was to determine which patients benefit the most from DIBH by comparing percent reduction in mean cardiac dose conferred by DIBH for patients treated with whole breast RT ± boost (WBRT) versus those receiving breast/chest wall plus regional nodal irradiation, including internal mammary chain (IMC) nodes (B/CWRT + RNI) using a modified wide tangent technique. A secondary objective was to determine if DIBH was required to meet a proposed heart dose constraint of Dmean < 4 Gy in these two cohorts. Twenty consecutive patients underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: WBRT (n = 11) and B/CWRT + RNI (n = 9). 3D-conformal plans were developed and FB was compared to DIBH for each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart and LAD dose, as well as lung V20 were compared between the two cohorts using Wilcox rank-sum testing. The significance level was set at 0.05 with Bonferroni correction for multiple testing. All patients had comparable target coverage on DIBH and FB. DIBH statistically significantly reduced mean heart and LAD dose for both cohorts. Percent reduction in mean heart and LAD dose with DIBH was significantly larger in the B/CWRT + RNI cohort compared to WBRT group (relative reduction in mean heart and LAD dose: 55.9 % and 72.1 % versus 29.2 % and 43.5 %, p < 0.02). All patients in the WBRT group and five patients (56 %) in the B/CWBRT + RNI group met heart Dmean <4 Gy with FB. All patients met this constraint with DIBH. All patients receiving WBRT met Dmean Heart < 4 Gy on FB, while only slightly over half of patients receiving B/CWRT + RNI were able to meet this constraint in FB. DIBH allowed a greater reduction in mean heart and LAD dose in patients receiving B/CWRT + RNI, including IMC nodes than patients receiving WBRT. These findings suggest greatest benefit from DIBH treatment for patients receiving regional nodal irradiation.

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

PubMed

Henne, Erik; Kesten, Steven; Herth, Felix J F

2013-01-01

A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile. Copyright © 2013 S. Karger AG, Basel.

Radiation dose management in thoracic CT: an international survey.

PubMed

Molinari, Francesco; Tack, Denis M; Boiselle, Philip; Ngo, Long; Mueller-Mang, Christina; Litmanovich, Diana; Bankier, Alexander A

2013-01-01

We aimed to examine current practice patterns of international thoracic radiologists regarding radiation dose management in adult thoracic computed tomography (CT) examinations. An electronic questionnaire was sent to 800 members of five thoracic radiology societies in North America, Europe, Asia, and Latin America addressing radiation dose training and education, standard kVp and mAs settings for thoracic CT, dose reduction practices, clinical scenarios, and demographics. Of the 800 radiologists, 146 responded to our survey. Nearly half (66/146, 45% [95% confidence interval, 37%-53%]) had no formal training in dose reduction, with "self-study of the literature" being the most common form of training (54/146, 37% [29%-45%]). One hundred and seventeen (80% [74%-87%]) had automatic exposure control, and 76 (65% [56%-74%]) used it in all patients. Notably, most respondents (89% [84%-94%]) used a 120 to 125 kVp standard setting, whereas none used 140 kVp. The most common average dose-length-product (DLP) value was 150 to 249 mGy.cm (75/146, 51% [43%-59%]), and 59% (51%-67%) delivered less than 250 mGy.cm in a 70 kg patient. There was a tendency towards higher DLP values with multidetector-row CT. Age, gender, and pregnancy were associated more with dose reduction than weight and clinical indication. Efforts for reducing patient radiation dose are highly prevalent among thoracic radiologists. Areas for improvement include reduction of default tube current settings, reduction of anatomical scan coverage, greater use of automatic exposure control, and eventually, reduction of current reference dose values. Our study emphasizes the need for international guidelines to foster greater conformity in dose reduction by thoracic radiologists.

Inability of populations of Callosobruchus maculatus to develop tolerance to exposures of acute gamma irradiation

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

Brower, J.H.

1974-03-01

The reproductive capacity and resistance to an acute dose of gamma irradiation were determined for populations of Callosobruchus maculatus treated with substerilizing doses of irradiation each generation for 30 generations. Reproductive capacity was decreased by an ancestral history of irradiation, the reduction being positively correlated with both the size of dose per generation and the number of ancestral generations treated. Irradiation of the selected populations with an acute dose revealed no increase in tolerance, even after 30 generations. In general, the greater the amount of accumulated ancestral exposure to irradiation, the greater the sensitivity to further irradiation. The ability tomore » develop a tolerance to ionizing irradiation may not be a general phenomenon in insects. (auth)« less

[Examination of patient dose reduction in cardiovasucular X-ray systems with a metal filter].

PubMed

Yasuda, Mitsuyoshi; Kato, Kyouichi; Tanabe, Nobuaki; Sakiyama, Koushi; Uchiyama, Yushi; Suzuki, Yoshiaki; Suzuki, Hiroshi; Nakazawa, Yasuo

2012-01-01

In interventional X-ray for cardiology of flat panel digital detector (FPD), the phenomenon that exposure dose was suddenly increased when a subject thickness was thickened was recognized. At that time, variable metal built-in filters in FPD were all off. Therefore, we examined whether dose reduction was possible without affecting a clinical image using metal filter (filter) which we have been conventionally using for dose reduction. About 45% dose reduction was achieved when we measured an exposure dose at 30 cm of acrylic thickness in the presence of a filter. In addition, we measured signal to noise ratio/contrast to noise ratio/a resolution limit by the visual evaluation, and there was no influence by filter usage. In the clinical examination, visual evaluation of image quality of coronary angiography (40 cases) using a 5-point evaluation scale by a physician was performed. As a result, filter usage did not influence the image quality (p=NS). Therefore, reduction of sudden increase of exposure dose was achieved without influencing an image quality by adding filter to FPD.

Impact of electronic health record-based, pharmacist-driven valganciclovir dose optimization in solid organ transplant recipients.

PubMed

Hensler, David; Richardson, Chad L; Brown, Joslyn; Tseng, Christine; DeCamp, Phyllis J; Yang, Amy; Pawlowski, Anna; Ho, Bing; Ison, Michael G

2018-04-01

Prophylaxis with valganciclovir reduces the incidence of cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under-dosing of valganciclovir is associated with an increased risk of CMV infection and development of ganciclovir-resistant CMV. An automated electronic health record (EHR)-based, pharmacist-driven program was developed to optimize dosing of valganciclovir in solid organ transplant recipients at a large transplant center. Two cohorts of kidney, pancreas-kidney, and liver transplant recipients from our center pre-implementation (April 2011-March 2012, n = 303) and post-implementation of the optimization program (September 2012-August 2013, n=263) had demographic and key outcomes data collected for 1 year post-transplant. The 1-year incidence of CMV infection dropped from 56 (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI 1.06-2.60, P = .027) for the pre-implementation group after adjusting for potential confounders. The program also resulted in a numerical reduction in the number of ganciclovir-resistant CMV cases (2 [0.7%] pre-implementation vs 0 post-implementation). An EHR-based, pharmacist-driven valganciclovir dose optimization program was associated with reduction in CMV infections. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation.

PubMed

Parihar, Vipan K; Pasha, Junaid; Tran, Katherine K; Craver, Brianna M; Acharya, Munjal M; Limoli, Charles L

2015-03-01

Cranial radiotherapy is used routinely to control the growth of primary and secondary brain tumors, but often results in serious and debilitating cognitive dysfunction. In part due to the beneficial dose depth distributions that may spare normal tissue damage, the use of protons to treat CNS and other tumor types is rapidly gaining popularity. Astronauts exposed to lower doses of protons in the space radiation environment are also at risk for developing adverse CNS complications. To explore the consequences of whole body proton irradiation, mice were subjected to 0.1 and 1 Gy and analyzed for morphometric changes in hippocampal neurons 10 and 30 days following exposure. Significant dose-dependent reductions (~33 %) in dendritic complexity were found, when dendritic length, branching and area were analyzed 30 days after exposure. At equivalent doses and times, significant reductions in the number (~30 %) and density (50-75 %) of dendritic spines along hippocampal neurons of the dentate gyrus were also observed. Immature spines (filopodia, long) exhibited the greatest sensitivity (1.5- to 3-fold) to irradiation, while more mature spines (mushroom) were more resistant to changes over a 1-month post-irradiation timeframe. Irradiated granule cell neurons spanning the subfields of the dentate gyrus showed significant and dose-responsive reductions in synaptophysin expression, while the expression of postsynaptic density protein (PSD-95) was increased significantly. These findings corroborate our past work using photon irradiation, and demonstrate for the first time, dose-responsive changes in dendritic complexity, spine density and morphology and synaptic protein levels following exposure to low-dose whole body proton irradiation.

Achieving routine submillisievert CT scanning: report from the summit on management of radiation dose in CT.

PubMed

McCollough, Cynthia H; Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I

2012-08-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation.

Standard pentostatin dose reductions in renal insufficiency are not adequate: selected patients with steroid-refractory acute graft-versus-host disease.

PubMed

Poi, Ming J; Hofmeister, Craig C; Johnston, Jeffrey S; Edwards, Ryan B; Jansak, Buffy S; Lucas, David M; Farag, Sherif S; Dalton, James T; Devine, Steven M; Grever, Michael R; Phelps, Mitch A

2013-08-01

Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose reduction equations for patients with renal insufficiency are based on few patients with limited pharmacokinetic and clinical results. This phase II study (NCT00201786) was conducted to assess pentostatin efficacy and infectious complications seen from our previous phase I study in steroid-refractory acute GVHD (aGVHD). Hospitalized patients with steroid-refractory aGVHD were given pentostatin 1.5 mg/m(2)/day intravenously on days 1-3 of each 14-day cycle. Prior to each dose, dose modifications were based on Cockcroft-Gault estimated creatinine clearance (eCrCL) with 30-50 mL/min/1.73 m(2) leading to a 50 % dose reduction and eCrCL less than 30 mL/min/1.73 m(2) leading to study removal. Plasma pentostatin area under the concentration-time curve (AUC) and incidence of infectious complications were evaluated. Two of the eight patients treated demonstrated excessive pentostatin exposure as determined by measurement of AUC. One of these patients had renal impairment, whereas the other patient demonstrated borderline renal function. Despite dose reduction to 0.75 mg/m(2), AUCs were significantly increased compared to the other patients in this study. Seven of eight patients treated with pentostatin had cytomegalovirus (CMV) viremia after pentostatin treatment; however none developed proven CMV disease. A 50 % dose reduction in patients with eCrCL 30-50 mL/min/1.73 m(2) seems reasonable. However, the eCrCL should be interpreted with extreme caution in patients who are critically ill and/or with poor performance status. Renal function assessment based on the Cockcroft-Gault method could be significantly overestimated thus risking pentostatin overdosing. These results imply a need to closely monitor pentostatin exposure in patients with renal insufficiency.

Analysis of dose rates received around the storage pool for irradiated control rods in a BWR nuclear power plant.

PubMed

Ródenas, J; Abarca, A; Gallardo, S

2011-08-01

BWR control rods are activated by neutron reactions in the reactor. The dose produced by this activity can affect workers in the area surrounding the storage pool, where activated rods are stored. Monte Carlo (MC) models for neutron activation and dose assessment around the storage pool have been developed and validated. In this work, the MC models are applied to verify the expected reduction of dose when the irradiated control rod is hanged in an inverted position into the pool. 2010 Elsevier Ltd. All rights reserved.

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong

2015-01-01

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch

PubMed Central

Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; González, Hans Guerrero; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-01-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate. PMID:24556354

Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

PubMed

Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-04-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

Relationship between radiation dose reduction and image quality change in photostimulable phosphor luminescence X-ray imaging systems.

PubMed

Sakurai, T; Kawamata, R; Kozai, Y; Kaku, Y; Nakamura, K; Saito, M; Wakao, H; Kashima, I

2010-05-01

The aim of the study was to clarify the change in image quality upon X-ray dose reduction and to re-analyse the possibility of X-ray dose reduction in photostimulable phosphor luminescence (PSPL) X-ray imaging systems. In addition, the study attempted to verify the usefulness of multiobjective frequency processing (MFP) and flexible noise control (FNC) for X-ray dose reduction. Three PSPL X-ray imaging systems were used in this study. Modulation transfer function (MTF), noise equivalent number of quanta (NEQ) and detective quantum efficiency (DQE) were evaluated to compare the basic physical performance of each system. Subjective visual evaluation of diagnostic ability for normal anatomical structures was performed. The NEQ, DQE and diagnostic ability were evaluated at base X-ray dose, and 1/3, 1/10 and 1/20 of the base X-ray dose. The MTF of the systems did not differ significantly. The NEQ and DQE did not necessarily depend on the pixel size of the system. The images from all three systems had a higher diagnostic utility compared with conventional film images at the base and 1/3 X-ray doses. The subjective image quality was better at the base X-ray dose than at 1/3 of the base dose in all systems. The MFP and FNC-processed images had a higher diagnostic utility than the images without MFP and FNC. The use of PSPL imaging systems may allow a reduction in the X-ray dose to one-third of that required for conventional film. It is suggested that MFP and FNC are useful for radiation dose reduction.

Temporal variation of dose rate distribution around the Fukushima Daiichi nuclear power station using unmanned helicopter.

PubMed

Sanada, Yukihisa; Orita, Tadashi; Torii, Tatsuo

2016-12-01

Aerial radiological survey using an unmanned aerial vehicle (UAV) was applied to measurement surface contamination around the Fukushima Daiichi nuclear power station (FDNPS). An unmanned helicopter monitoring system (UHMS) was developed to survey the environmental effect of radioactive cesium scattered as a result of the FDNPS accident. The UHMS was used to monitor the area surrounding the FDNPS six times from 2012 to 2015. Quantitative changes in the radioactivity distribution trend were revealed from the results of these monitoring runs. With this information, we found that the actual reduction of dose rate was faster than the one calculated with radiocesium physical half-life. It is indicated that the attenuation effect of radiation by radiocesium penetration in soil is dominant as for reason of reduction of dose rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

PubMed

Kourlaba, Georgia; Dimopoulos, Meletios A; Pectasides, Dimitrios; Skarlos, Dimosthenis V; Gogas, Helen; Pentheroudakis, George; Koutras, Angelos; Fountzilas, George; Maniadakis, Nikos

2015-07-01

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

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

Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

1995-03-01

In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

A quantitative comparison of noise reduction across five commercial (hybrid and model-based) iterative reconstruction techniques: an anthropomorphic phantom study.

PubMed

Patino, Manuel; Fuentes, Jorge M; Hayano, Koichi; Kambadakone, Avinash R; Uyeda, Jennifer W; Sahani, Dushyant V

2015-02-01

OBJECTIVE. The objective of our study was to compare the performance of three hybrid iterative reconstruction techniques (IRTs) (ASiR, iDose4, SAFIRE) and their respective strengths for image noise reduction on low-dose CT examinations using filtered back projection (FBP) as the standard reference. Also, we compared the performance of these three hybrid IRTs with two model-based IRTs (Veo and IMR) for image noise reduction on low-dose examinations. MATERIALS AND METHODS. An anthropomorphic abdomen phantom was scanned at 100 and 120 kVp and different tube current-exposure time products (25-100 mAs) on three CT systems (for ASiR and Veo, Discovery CT750 HD; for iDose4 and IMR, Brilliance iCT; and for SAFIRE, Somatom Definition Flash). Images were reconstructed using FBP and using IRTs at various strengths. Nine noise measurements (mean ROI size, 423 mm(2)) on extracolonic fat for the different strengths of IRTs were recorded and compared with FBP using ANOVA. Radiation dose, which was measured as the volume CT dose index and dose-length product, was also compared. RESULTS. There were no significant differences in radiation dose and image noise among the scanners when FBP was used (p > 0.05). Gradual image noise reduction was observed with each increasing increment of hybrid IRT strength, with a maximum noise suppression of approximately 50% (48.2-53.9%). Similar noise reduction was achieved on the scanners by applying specific hybrid IRT strengths. Maximum noise reduction was higher on model-based IRTs (68.3-81.1%) than hybrid IRTs (48.2-53.9%) (p < 0.05). CONCLUSION. When constant scanning parameters are used, radiation dose and image noise on FBP are similar for CT scanners made by different manufacturers. Significant image noise reduction is achieved on low-dose CT examinations rendered with IRTs. The image noise on various scanners can be matched by applying specific hybrid IRT strengths. Model-based IRTs attain substantially higher noise reduction than hybrid IRTs irrespective of the radiation dose.

Initial apixaban dosing in patients with atrial fibrillation.

PubMed

Buchholz, Alexander; Ueberham, Laura; Gorczynska, Kaja; Dinov, Borislav; Hilbert, Sebastian; Dagres, Nikolaos; Husser, Daniela; Hindricks, Gerhard; Bollmann, Andreas

2018-05-01

Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing-relevant secondary diagnoses and co-medication. We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664-0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076-1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881-0.940, P < 0.0001) were independent predictors for apixaban underdosage. In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction. © 2018 Wiley Periodicals, Inc.

Effect of Edge-Preserving Adaptive Image Filter on Low-Contrast Detectability in CT Systems: Application of ROC Analysis

PubMed Central

Okumura, Miwa; Ota, Takamasa; Kainuma, Kazuhisa; Sayre, James W.; McNitt-Gray, Michael; Katada, Kazuhiro

2008-01-01

Objective. For the multislice CT (MSCT) systems with a larger number of detector rows, it is essential to employ dose-reduction techniques. As reported in previous studies, edge-preserving adaptive image filters, which selectively eliminate only the noise elements that are increased when the radiation dose is reduced without affecting the sharpness of images, have been developed. In the present study, we employed receiver operating characteristic (ROC) analysis to assess the effects of the quantum denoising system (QDS), which is an edge-preserving adaptive filter that we have developed, on low-contrast resolution, and to evaluate to what degree the radiation dose can be reduced while maintaining acceptable low-contrast resolution. Materials and Methods. The low-contrast phantoms (Catphan 412) were scanned at various tube current settings, and ROC analysis was then performed for the groups of images obtained with/without the use of QDS at each tube current to determine whether or not a target could be identified. The tube current settings for which the area under the ROC curve (Az value) was approximately 0.7 were determined for both groups of images with/without the use of QDS. Then, the radiation dose reduction ratio when QDS was used was calculated by converting the determined tube current to the radiation dose. Results. The use of the QDS edge-preserving adaptive image filter allowed the radiation dose to be reduced by up to 38%. Conclusion. The QDS was found to be useful for reducing the radiation dose without affecting the low-contrast resolution in MSCT studies. PMID:19043565

RADTRAD: A simplified model for RADionuclide Transport and Removal And Dose estimation

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

Humphreys, S.L.; Miller, L.A.; Monroe, D.K.

1998-04-01

This report documents the RADTRAD computer code developed for the U.S. Nuclear Regulatory Commission (NRC) Office of Nuclear Reactor Regulation (NRR) to estimate transport and removal of radionuclides and dose at selected receptors. The document includes a users` guide to the code, a description of the technical basis for the code, the quality assurance and code acceptance testing documentation, and a programmers` guide. The RADTRAD code can be used to estimate the containment release using either the NRC TID-14844 or NUREG-1465 source terms and assumptions, or a user-specified table. In addition, the code can account for a reduction in themore » quantity of radioactive material due to containment sprays, natural deposition, filters, and other natural and engineered safety features. The RADTRAD code uses a combination of tables and/or numerical models of source term reduction phenomena to determine the time-dependent dose at user-specified locations for a given accident scenario. The code system also provides the inventory, decay chain, and dose conversion factor tables needed for the dose calculation. The RADTRAD code can be used to assess occupational radiation exposures, typically in the control room; to estimate site boundary doses; and to estimate dose attenuation due to modification of a facility or accident sequence.« less

Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.

PubMed

Pasi, K John; Rangarajan, Savita; Georgiev, Pencho; Mant, Tim; Creagh, Michael D; Lissitchkov, Toshko; Bevan, David; Austin, Steve; Hay, Charles R; Hegemann, Inga; Kazmi, Rashid; Chowdary, Pratima; Gercheva-Kyuchukova, Liana; Mamonov, Vasily; Timofeeva, Margarita; Soh, Chang-Heok; Garg, Pushkal; Vaishnaw, Akshay; Akinc, Akin; Sørensen, Benny; Ragni, Margaret V

2017-08-31

Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations. In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran. No thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants. Once-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .).

Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

2017-03-01

This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

Radiation dose-reduction strategies in thoracic CT.

PubMed

Moser, J B; Sheard, S L; Edyvean, S; Vlahos, I

2017-05-01

Modern computed tomography (CT) machines have the capability to perform thoracic CT for a range of clinical indications at increasingly low radiation doses. This article reviews several factors, both technical and patient-related, that can affect radiation dose and discusses current dose-reduction methods relevant to thoracic imaging through a review of current techniques in CT acquisition and image reconstruction. The fine balance between low radiation dose and high image quality is considered throughout, with an emphasis on obtaining diagnostic quality imaging at the lowest achievable radiation dose. The risks of excessive radiation dose reduction are also considered. Inappropriately low dose may result in suboptimal or non-diagnostic imaging that may reduce diagnostic confidence, impair diagnosis, or result in repeat examinations incurring incremental ionising radiation exposure. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

PubMed Central

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai

2017-01-01

Abstract Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction. PMID:29281130

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.

Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study.

PubMed

Kim, Soo Hyun; Jung, Seung Eun; Oh, Sang Hoon; Park, Kyu Nam; Youn, Chun Song

2011-11-03

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

SU-E-T-329: Dosimetric Impact of Implementing Metal Artifact Reduction Methods and Metal Energy Deposition Kernels for Photon Dose Calculations

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

Huang, J; Followill, D; Howell, R

2015-06-15

Purpose: To investigate two strategies for reducing dose calculation errors near metal implants: use of CT metal artifact reduction methods and implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) method. Methods: Radiochromic film was used to measure the dose upstream and downstream of titanium and Cerrobend implants. To assess the dosimetric impact of metal artifact reduction methods, dose calculations were performed using baseline, uncorrected images and metal artifact reduction Methods: Philips O-MAR, GE’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI imaging with metal artifact reduction software applied (MARs).To assess the impact of metal kernels, titaniummore » and silver kernels were implemented into a commercial collapsed cone C/S algorithm. Results: The CT artifact reduction methods were more successful for titanium than Cerrobend. Interestingly, for beams traversing the metal implant, we found that errors in the dimensions of the metal in the CT images were more important for dose calculation accuracy than reduction of imaging artifacts. The MARs algorithm caused a distortion in the shape of the titanium implant that substantially worsened the calculation accuracy. In comparison to water kernel dose calculations, metal kernels resulted in better modeling of the increased backscatter dose at the upstream interface but decreased accuracy directly downstream of the metal. We also found that the success of metal kernels was dependent on dose grid size, with smaller calculation voxels giving better accuracy. Conclusion: Our study yielded mixed results, with neither the metal artifact reduction methods nor the metal kernels being globally effective at improving dose calculation accuracy. However, some successes were observed. The MARs algorithm decreased errors downstream of Cerrobend by a factor of two, and metal kernels resulted in more accurate backscatter dose upstream of metals. Thus, these two strategies do have the potential to improve accuracy for patients with metal implants in certain scenarios. This work was supported by Public Health Service grants CA 180803 and CA 10953 awarded by the National Cancer Institute, United States of Health and Human Services, and in part by Mobius Medical Systems.« less

Half-Fan-Based Intensity-Weighted Region-of-Interest Imaging for Low-Dose Cone-Beam CT in Image-Guided Radiation Therapy.

PubMed

Yoo, Boyeol; Son, Kihong; Pua, Rizza; Kim, Jinsung; Solodov, Alexander; Cho, Seungryong

2016-10-01

With the increased use of computed tomography (CT) in clinics, dose reduction is the most important feature people seek when considering new CT techniques or applications. We developed an intensity-weighted region-of-interest (IWROI) imaging method in an exact half-fan geometry to reduce the imaging radiation dose to patients in cone-beam CT (CBCT) for image-guided radiation therapy (IGRT). While dose reduction is highly desirable, preserving the high-quality images of the ROI is also important for target localization in IGRT. An intensity-weighting (IW) filter made of copper was mounted in place of a bowtie filter on the X-ray tube unit of an on-board imager (OBI) system such that the filter can substantially reduce radiation exposure to the outer ROI. In addition to mounting the IW filter, the lead-blade collimation of the OBI was adjusted to produce an exact half-fan scanning geometry for a further reduction of the radiation dose. The chord-based rebinned backprojection-filtration (BPF) algorithm in circular CBCT was implemented for image reconstruction, and a humanoid pelvis phantom was used for the IWROI imaging experiment. The IWROI image of the phantom was successfully reconstructed after beam-quality correction, and it was registered to the reference image within an acceptable level of tolerance. Dosimetric measurements revealed that the dose is reduced by approximately 61% in the inner ROI and by 73% in the outer ROI compared to the conventional bowtie filter-based half-fan scan. The IWROI method substantially reduces the imaging radiation dose and provides reconstructed images with an acceptable level of quality for patient setup and target localization. The proposed half-fan-based IWROI imaging technique can add a valuable option to CBCT in IGRT applications.

Achieving Routine Submillisievert CT Scanning: Report from the Summit on Management of Radiation Dose in CT

PubMed Central

Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I.

2012-01-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation. © RSNA, 2012 PMID:22692035

SU-C-207-05: A Comparative Study of Noise-Reduction Algorithms for Low-Dose Cone-Beam Computed Tomography

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

Mukherjee, S; Yao, W

2015-06-15

Purpose: To study different noise-reduction algorithms and to improve the image quality of low dose cone beam CT for patient positioning in radiation therapy. Methods: In low-dose cone-beam CT, the reconstructed image is contaminated with excessive quantum noise. In this study, three well-developed noise reduction algorithms namely, a) penalized weighted least square (PWLS) method, b) split-Bregman total variation (TV) method, and c) compressed sensing (CS) method were studied and applied to the images of a computer–simulated “Shepp-Logan” phantom and a physical CATPHAN phantom. Up to 20% additive Gaussian noise was added to the Shepp-Logan phantom. The CATPHAN phantom was scannedmore » by a Varian OBI system with 100 kVp, 4 ms and 20 mA. For comparing the performance of these algorithms, peak signal-to-noise ratio (PSNR) of the denoised images was computed. Results: The algorithms were shown to have the potential in reducing the noise level for low-dose CBCT images. For Shepp-Logan phantom, an improvement of PSNR of 2 dB, 3.1 dB and 4 dB was observed using PWLS, TV and CS respectively, while for CATPHAN, the improvement was 1.2 dB, 1.8 dB and 2.1 dB, respectively. Conclusion: Penalized weighted least square, total variation and compressed sensing methods were studied and compared for reducing the noise on a simulated phantom and a physical phantom scanned by low-dose CBCT. The techniques have shown promising results for noise reduction in terms of PSNR improvement. However, reducing the noise without compromising the smoothness and resolution of the image needs more extensive research.« less

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

PubMed Central

Smith, Daniel L.; Robertson, Henry; Desmond, Renee; Nagy, Tim R.; Allison, David B.

2010-01-01

Objective The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. Results & Conclusion Using data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate. PMID:21079617

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

PubMed Central

Gilbert, Mary E.; Sui, Li

2008-01-01

Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

Dose response of surfactants to attenuate gas embolism related platelet aggregation

NASA Astrophysics Data System (ADS)

Eckmann, David M.; Eckmann, Yonaton Y.; Tomczyk, Nancy

2014-03-01

Intravascular gas embolism promotes blood clot formation, cellular activation, and adhesion events, particularly with platelets. Populating the interface with surfactants is a chemical-based intervention to reduce injury from gas embolism. We studied platelet activation and platelet aggregation, prominent adverse responses to blood contact with bubbles. We examined dose-response relationships for two chemically distinct surfactants to attenuate the rise in platelet function stimulated by exposure to microbubbles. Significant reduction in platelet aggregation and platelet activation occurred with increasing concentration of the surfactants, indicating presence of a saturable system. A population balance model for platelet aggregation in the presence of embolism bubbles and surfactants was developed. Monte Carlo simulations for platelet aggregation were performed. Results agree qualitatively with experimental findings. Surfactant dose-dependent reductions in platelet activation and aggregation indicate inhibition of the gas/liquid interface's ability to stimulate cellular activation mechanically.

Restored low-dose digital breast tomosynthesis: a perception study

NASA Astrophysics Data System (ADS)

Borges, Lucas R.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2018-03-01

This work investigates the perception of noise from restored low-dose digital breast tomosynthesis (DBT) images. First, low-dose DBT projections were generated using a dose reduction simulation algorithm. A dataset of clinical images from the Hospital of the University of Pennsylvania was used for this purpose. Low-dose projections were then denoised with a denoising pipeline developed specifically for DBT images. Denoised and noisy projections were combined to generate images with signal-to-noise ratio comparable to the full-dose images. The quality of restored low-dose and full-dose projections were first compared in terms of an objective no-reference image quality metric previously validated for mammography. In the second analysis, regions of interest (ROIs) were selected from reconstructed full-dose and restored low-dose slices, and were displayed side-by-side on a high-resolution medical display. Five medical physics specialists were asked to choose the image containing less noise and less blur using a 2-AFC experiment. The objective metric shows that, after the proposed image restoration framework was applied, images with as little as 60% of the AEC dose yielded similar quality indices when compared to images acquired with the full-dose. In the 2-AFC experiments results showed that when the denoising framework was used, 30% reduction in dose was possible without any perceived difference in noise or blur. Note that this study evaluated the observers perception to noise and blur and does not claim that the dose of DBT examinations can be reduced with no harm to the detection of cancer. Future work is necessary to make any claims regarding detection, localization and characterization of lesions.

Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature.

PubMed

Zheng, Yulong; Fang, Weijia; Xu, Nong

2012-12-01

Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib dose-reduction was initiated. HFS may occur with icotinib, especially when administered in high doses.

MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology

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

NONE

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Toward assessing the diagnostic influence of dose reduction in pediatric CT: a study based on simulated lung nodules

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; DeLong, David M.; Jones, Robert P.; Colsher, James G.; Frush, Donald P.

2008-03-01

The purpose of this study is to evaluate the effect of reduced tube current, as a surrogate for radiation dose, on lung nodule detection in pediatric chest multi-detector CT (MDCT). Normal chest MDCT images of 13 patients aged 1 to 7 years old were used as templates for this study. The original tube currents were between 70 mA and 180 mA. Using proprietary noise addition software, noise was added to the images to create 13 cases at the lowest common mA (i.e. 70 mA), 13 cases at 35 mA (50% reduction), and 13 cases at 17.5 mA (75% reduction). Three copies of each case were made for a total of 117 series for simulated nodule insertion. A technique for three-dimensional simulation of small lung nodules was developed, validated through an observer study, and used to add nodules to the series. Care was taken to ensure that each of three lung zones (upper, middle, lower) contained 0 or 1 nodule. The series were randomized and the presence of a nodule in each lung zone was rated independently and blindly by three pediatric radiologists on a continuous scale between 0 (definitely absent) and 100 (definitely present). Receiver operating characteristic analysis of the data showed no general significant difference in diagnostic accuracy between the reduced mA values and 70 mA, suggesting a potential for dose reduction with preserved diagnostic quality. To our knowledge, this study is the first controlled, systematic, and task-specific assessment of the influence of dose reduction in pediatric chest CT.

Novel shielding materials for space and air travel.

PubMed

Vana, N; Hajek, M; Berger, T; Fugger, M; Hofmann, P

2006-01-01

The reduction of dose onboard spacecraft and aircraft by appropriate shielding measures plays an essential role in the future development of space exploration and air travel. The design of novel shielding strategies and materials may involve hydrogenous composites, as it is well known that liquid hydrogen is most effective in attenuating charged particle radiation. As precursor for a later flight experiment, the shielding properties of newly developed hydrogen-rich polymers and rare earth-doped high-density rubber were tested in various ground-based neutron and heavy ion fields and compared with aluminium and polyethylene as reference materials. Absorbed dose, average linear energy transfer and gamma-equivalent neutron absorbed dose were determined by means of LiF:Mg,Ti thermoluminescence dosemeters and CR-39 plastic nuclear track detectors. First results for samples of equal aerial density indicate that selected hydrogen-rich plastics and rare-earth-doped rubber may be more effective in attenuating cosmic rays by up to 10% compared with conventional aluminium shielding. The appropriate adaptation of shielding thicknesses may thus allow reducing the biologically relevant dose. Owing to the lower density of the plastic composites, mass savings shall result in a significant reduction of launch costs. The experiment was flown as part of the European Space Agency's Biopan-5 mission in May 2005.

The Acute and Chronic Effects of the Novel Anticonvulsant Lacosamide in an Experimental Model of Status Epilepticus

PubMed Central

Wasterlain, Claude G.; Stöhr, Thomas; Matagne, Alain

2011-01-01

The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50 mg/kg) either 10 minutes (early treatment) or 40 minutes (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend towards reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50 mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P <0.05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures.. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies. PMID:21277168

Microglial disruption in young mice with early chronic lead exposure☆

PubMed Central

Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali; Schaub, Tanner; Cervantes, Miguel; Armijos, Rodrigo X.

2013-01-01

The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals. PMID:23598043

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

PubMed Central

Conover, Christine F.; Beggs, Luke A.; Beck, Darren T.; Otzel, Dana M.; Balaez, Alexander; Combs, Sarah M.; Miller, Julie R.; Ye, Fan; Aguirre, J. Ignacio; Neuville, Kathleen G.; Williams, Alyssa A.; Conrad, Bryan P.; Gregory, Chris M.; Wronski, Thomas J.; Bose, Prodip K.; Borst, Stephen E.

2014-01-01

Abstract Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77–85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13–27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit. Testosterone-induced prostate enlargement, however, represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI. PMID:24378197

Biological uptake of polychlorinated biphenyls by Macoma balthica from sediment amended with activated carbon

USGS Publications Warehouse

McLeod, Pamela B.; van den Heuvel-Greve, Martine J.; Luoma, S.N.; Luthy, R.G.

2007-01-01

This work characterizes the efficacy of activated carbon amendment in reducing polychlorinated biphenyl (PCB) bioavailability to clams (Macoma balthica) from field-contaminated sediment (Hunters Point Naval Shipyard, San Francisco Bay, CA, USA) Test methods were developed for the use of clams to investigate the effects of sediment amendment on biological uptake. Sediment was mixed with activated carbon for one month. Bioaccumulation tests (28 d) were employed to assess the relationships between carbon dose and carbon particle size on observed reductions in clam biological uptake of PCBs. Extraction and cleanup protocols were developed for the clam tissue. Efficacy of activated carbon treatment was found to increase with both increasing carbon dose and decreasing carbon particle size. Average reductions in bioaccumulation of 22, 64, and 84% relative to untreated Hunters Point sediment were observed for carbon amendments of 0.34, 1.7, and 3.4%, respectively. Average bioaccumulation reductions of 41, 73, and 89% were observed for amendments (dose = 1.7% dry wt) with carbon particles of 180 to 250, 75 to 180, and 25 to 75 ??m, respectively, in diameter, indicating kinetic phenomena in these tests. Additionally, a biodynamic model quantifying clam PCB uptake from water and sediment as well as loss through elimination provided a good fit of experimental data. Model predictions suggest that the sediment ingestion route contributed 80 to 95% of the PCB burdens in the clams. ?? 2007 SETAC.

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

PubMed

Noël, Peter B; Engels, Stephan; Köhler, Thomas; Muenzel, Daniela; Franz, Daniela; Rasper, Michael; Rummeny, Ernst J; Dobritz, Martin; Fingerle, Alexander A

2018-01-01

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose 4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

Analysis of esophageal-sparing treatment plans for patients with high-grade esophagitis.

PubMed

Niedzielski, Joshua; Bluett, Jaques B; Williamson, Ryan T; Liao, Zhongxing; Gomez, Daniel R; Court, Laurence E

2013-07-08

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11-beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three-dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm(3), respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans' mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm(3), respectively, compared with the clinical plans. The normalized plans' mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints.

Analysis of esophageal‐sparing treatment plans for patients with high‐grade esophagitis

PubMed Central

Bluett, Jaques B.; Williamson, Ryan T.; Liao, Zhongxing; Gomez, Daniel R.; Court, Laurence E.

2013-01-01

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11‐beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three‐dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm3, respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans’ mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm3, respectively, compared with the clinical plans. The normalized plans’ mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints. PACS number: 87.53 Tf PMID:23835390

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

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

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

Validation of CT dose-reduction simulation

PubMed Central

Massoumzadeh, Parinaz; Don, Steven; Hildebolt, Charles F.; Bae, Kyongtae T.; Whiting, Bruce R.

2009-01-01

The objective of this research was to develop and validate a custom computed tomography dose-reduction simulation technique for producing images that have an appearance consistent with the same scan performed at a lower mAs (with fixed kVp, rotation time, and collimation). Synthetic noise is added to projection (sinogram) data, incorporating a stochastic noise model that includes energy-integrating detectors, tube-current modulation, bowtie beam filtering, and electronic system noise. Experimental methods were developed to determine the parameters required for each component of the noise model. As a validation, the outputs of the simulations were compared to measurements with cadavers in the image domain and with phantoms in both the sinogram and image domain, using an unbiased root-mean-square relative error metric to quantify agreement in noise processes. Four-alternative forced-choice (4AFC) observer studies were conducted to confirm the realistic appearance of simulated noise, and the effects of various system model components on visual noise were studied. The “just noticeable difference (JND)” in noise levels was analyzed to determine the sensitivity of observers to changes in noise level. Individual detector measurements were shown to be normally distributed (p>0.54), justifying the use of a Gaussian random noise generator for simulations. Phantom tests showed the ability to match original and simulated noise variance in the sinogram domain to within 5.6%±1.6% (standard deviation), which was then propagated into the image domain with errors less than 4.1%±1.6%. Cadaver measurements indicated that image noise was matched to within 2.6%±2.0%. More importantly, the 4AFC observer studies indicated that the simulated images were realistic, i.e., no detectable difference between simulated and original images (p=0.86) was observed. JND studies indicated that observers’ sensitivity to change in noise levels corresponded to a 25% difference in dose, which is far larger than the noise accuracy achieved by simulation. In summary, the dose-reduction simulation tool demonstrated excellent accuracy in providing realistic images. The methodology promises to be a useful tool for researchers and radiologists to explore dose reduction protocols in an effort to produce diagnostic images with radiation dose “as low as reasonably achievable.” PMID:19235386

Efficacy of granulocyte colony stimulating factor as a secondary prophylaxis along with full-dose chemotherapy following a prior cycle of febrile neutropenia.

PubMed

Gupta, Seema; Singh, Pankaj K; Bhatt, Madan L B; Pant, Mohan C; Gupta, Rajeev; Negi, Mahendra P S

2010-10-01

Secondary prophylaxis with recombinant human granulocyte colony stimulating factor (G-CSF) is recommended where patients have experienced febrile neutropenia in an earlier chemotherapy cycle and for whom the maintenance of chemotherapy dose intensity is important; or where febrile neutropenia has not occurred but prolonged neutropenia is causing excessive dose delay or reduction, where maintenance of dose intensity is important. The objective of this study was to determine the efficacy and feasibility of G-CSF as secondary prophylaxis when used along with full dose moderately myelotoxic chemotherapy following a prior cycle with febrile-neutropenia. Fifty-two patients aged 22-75 years with febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with support of filgrastim 24 h after completion of chemotherapy (300 μg/day/subcutaneously (s.c.) for weight < 60 kg, 480 μg/day/s.c. for weight > 60 kg, for at least 10 consecutive days), patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. The use of the hematopoietic growth factor G-CSF was shown to shorten the neutrophil recovery time, resulting in significant reduction of incidence of febrile neutropenia, hospitalization and use of broad spectrum antibiotics. There was no drug related death or adverse events associated with either cycle. In conclusion, recombinant human G-CSF is effective and relatively safe as a secondary prophylaxis with full dose chemotherapy in patients who develop febrile neutropenia following prior cycles of moderately myelotoxic chemotherapy.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Method for inserting noise in digital mammography to simulate reduction in radiation dose

NASA Astrophysics Data System (ADS)

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Vieira, Marcelo A. C.

2015-03-01

The quality of clinical x-ray images is closely related to the radiation dose used in the imaging study. The general principle for selecting the radiation is ALARA ("as low as reasonably achievable"). The practical optimization, however, remains challenging. It is well known that reducing the radiation dose increases the quantum noise, which could compromise the image quality. In order to conduct studies about dose reduction in mammography, it would be necessary to acquire repeated clinical images, from the same patient, with different dose levels. However, such practice would be unethical due to radiation related risks. One solution is to simulate the effects of dose reduction in clinical images. This work proposes a new method, based on the Anscombe transformation, which simulates dose reduction in digital mammography by inserting quantum noise into clinical mammograms acquired with the standard radiation dose. Thus, it is possible to simulate different levels of radiation doses without exposing the patient to new levels of radiation. Results showed that the achieved quality of simulated images generated with our method is the same as when using other methods found in the literature, with the novelty of using the Anscombe transformation for converting signal-independent Gaussian noise into signal-dependent quantum noise.

Pediatric CT: implementation of ASIR for substantial radiation dose reduction while maintaining pre-ASIR image noise.

PubMed

Brady, Samuel L; Moore, Bria M; Yee, Brian S; Kaufman, Robert A

2014-01-01

To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current-modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. © RSNA, 2013.

SparseCT: interrupted-beam acquisition and sparse reconstruction for radiation dose reduction

NASA Astrophysics Data System (ADS)

Koesters, Thomas; Knoll, Florian; Sodickson, Aaron; Sodickson, Daniel K.; Otazo, Ricardo

2017-03-01

State-of-the-art low-dose CT methods reduce the x-ray tube current and use iterative reconstruction methods to denoise the resulting images. However, due to compromises between denoising and image quality, only moderate dose reductions up to 30-40% are accepted in clinical practice. An alternative approach is to reduce the number of x-ray projections and use compressed sensing to reconstruct the full-tube-current undersampled data. This idea was recognized in the early days of compressed sensing and proposals for CT dose reduction appeared soon afterwards. However, no practical means of undersampling has yet been demonstrated in the challenging environment of a rapidly rotating CT gantry. In this work, we propose a moving multislit collimator as a practical incoherent undersampling scheme for compressed sensing CT and evaluate its application for radiation dose reduction. The proposed collimator is composed of narrow slits and moves linearly along the slice dimension (z), to interrupt the incident beam in different slices for each x-ray tube angle (θ). The reduced projection dataset is then reconstructed using a sparse approach, where 3D image gradients are employed to enforce sparsity. The effects of the collimator slits on the beam profile were measured and represented as a continuous slice profile. SparseCT was tested using retrospective undersampling and compared against commercial current-reduction techniques on phantoms and in vivo studies. Initial results suggest that SparseCT may enable higher performance than current-reduction, particularly for high dose reduction factors.

Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults

PubMed Central

Troy, Stephanie B.; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

2015-01-01

Background. Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. Methods. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Results. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. Conclusions. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. PMID:25567841

ANI/MAELU engineering inspection criteria 8.3 ALARA

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

Schneider, L.

1995-03-01

The purpose of this criteria section is to provide guidelines for programs whose intent is to achieve occupational doses and doses to members of the public that are as low as is reasonably achievable (ALARA). The success that has been achieved by applying ALARA concepts at nuclear power plants is clearly illustrated by the major reductions in the annual cumulative dose to workers at many sites over the last few years. This success is the combined result of the general maturity of the nuclear industry, the intensive study of dose reduction practices by industry groups, and the successful sharing ofmore » experience and practices among plants. Source term reduction should be used as a primary ALARA mechanism. Methods which should be considered include: satellite and cobalt reduction, chemistry control, decontamination, submicron filters, zinc addition, hot spot reduction and permanent or temporary shielding.« less

Computational and human observer image quality evaluation of low dose, knowledge-based CT iterative reconstruction

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

Eck, Brendan L.; Fahmi, Rachid; Miao, Jun

2015-10-15

Purpose: Aims in this study are to (1) develop a computational model observer which reliably tracks the detectability of human observers in low dose computed tomography (CT) images reconstructed with knowledge-based iterative reconstruction (IMR™, Philips Healthcare) and filtered back projection (FBP) across a range of independent variables, (2) use the model to evaluate detectability trends across reconstructions and make predictions of human observer detectability, and (3) perform human observer studies based on model predictions to demonstrate applications of the model in CT imaging. Methods: Detectability (d′) was evaluated in phantom studies across a range of conditions. Images were generated usingmore » a numerical CT simulator. Trained observers performed 4-alternative forced choice (4-AFC) experiments across dose (1.3, 2.7, 4.0 mGy), pin size (4, 6, 8 mm), contrast (0.3%, 0.5%, 1.0%), and reconstruction (FBP, IMR), at fixed display window. A five-channel Laguerre–Gauss channelized Hotelling observer (CHO) was developed with internal noise added to the decision variable and/or to channel outputs, creating six different internal noise models. Semianalytic internal noise computation was tested against Monte Carlo and used to accelerate internal noise parameter optimization. Model parameters were estimated from all experiments at once using maximum likelihood on the probability correct, P{sub C}. Akaike information criterion (AIC) was used to compare models of different orders. The best model was selected according to AIC and used to predict detectability in blended FBP-IMR images, analyze trends in IMR detectability improvements, and predict dose savings with IMR. Predicted dose savings were compared against 4-AFC study results using physical CT phantom images. Results: Detection in IMR was greater than FBP in all tested conditions. The CHO with internal noise proportional to channel output standard deviations, Model-k4, showed the best trade-off between fit and model complexity according to AIC{sub c}. With parameters fixed, the model reasonably predicted detectability of human observers in blended FBP-IMR images. Semianalytic internal noise computation gave results equivalent to Monte Carlo, greatly speeding parameter estimation. Using Model-k4, the authors found an average detectability improvement of 2.7 ± 0.4 times that of FBP. IMR showed greater improvements in detectability with larger signals and relatively consistent improvements across signal contrast and x-ray dose. In the phantom tested, Model-k4 predicted an 82% dose reduction compared to FBP, verified with physical CT scans at 80% reduced dose. Conclusions: IMR improves detectability over FBP and may enable significant dose reductions. A channelized Hotelling observer with internal noise proportional to channel output standard deviation agreed well with human observers across a wide range of variables, even across reconstructions with drastically different image characteristics. Utility of the model observer was demonstrated by predicting the effect of image processing (blending), analyzing detectability improvements with IMR across dose, size, and contrast, and in guiding real CT scan dose reduction experiments. Such a model observer can be applied in optimizing parameters in advanced iterative reconstruction algorithms as well as guiding dose reduction protocols in physical CT experiments.« less

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Analysis of Compton continuum measurements

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

Gold, R.; Olson, I. K.

1970-01-01

Five computer programs: COMPSCAT, FEND, GABCO, DOSE, and COMPLOT, have been developed and used for the analysis and subsequent reduction of measured energy distributions of Compton recoil electrons to continuous gamma spectra. In addition to detailed descriptions of these computer programs, the relationship amongst these codes is stressed. The manner in which these programs function is illustrated by tracing a sample measurement through a complete cycle of the data-reduction process.

Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

PubMed

Utreja, Puneet; Jain, Subheet; Yadav, Subodh; Khandhuja, K L; Tiwary, A K

2011-11-01

In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

TU-F-CAMPUS-J-04: Evaluation of Metal Artifact Reduction Technique for the Radiation Therapy Planning

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

Jeong, K; Kuo, H; Ritter, J

Purpose: To evaluate the feasibility of using a metal artifact reduction technique in depleting metal artifact and its application in improving dose calculation in External Radiation Therapy Planning. Methods: CIRS electron density phantom was scanned with and without steel drill bits placed in some plug holes. Meta artifact reduction software with Metal Deletion Technique (MDT) was used to remove metal artifacts for scanned image with metal. Hounsfield units of electron density plugs from artifact free reference image and MDT processed images were compared. To test the dose calculation improvement after the MDT processed images, clinically approved head and neck planmore » with manual dental artifact correction was tested. Patient images were exported and processed with MDT and plan was recalculated with new MDT image without manual correction. Dose profiles near the metal artifacts were compared. Results: The MDT used in this study effectively reduced the metal artifact caused by beam hardening and scatter. The windmill around the metal drill was greatly improved with smooth rounded view. Difference of the mean HU in each density plug between reference and MDT images were less than 10 HU in most of the plugs. Dose difference between original plan and MDT images were minimal. Conclusion: Most metal artifact reduction methods were developed for diagnostic improvement purpose. Hence Hounsfield unit accuracy was not rigorously tested before. In our test, MDT effectively eliminated metal artifacts with good HU reproduciblity. However, it can introduce new mild artifacts so the MDT images should be checked with original images.« less

Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

PubMed

Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

2016-01-01

Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose-reduced datasets based on clinical (18)F-FDG PET data demonstrated the clinical applicability of the proposed data. Simulation of PET tracer dose reduction is possible with retrospective undersampling of list-mode data. Resulting simulated low-dose images have equivalent characteristics with PET images actually measured at lower doses and can be used to derive optimal tracer dose regimes.

Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

PubMed

Nguyen, Huynh; Morgan, David A F; Forwood, Mark R

2007-01-01

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10(-6). The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

PubMed

Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

2008-01-01

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

SU-F-J-48: Effect of Scan Length On Magnitude of Imaging Dose in KV CBCT

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

Deshpande, S; Naidu, S; Sutar, A

Purpose: To study effect of scan length on magnitude of imaging dose deposition in Varian kV CBCT for head & neck and pelvis CBCT. Methods: To study effect of scan length we measured imaging dose at depth of 8 cm for head and neck Cone Beam Computed Tomography (CBCT) acquisition ( X ray beam energy is used 100kV and 200 degree of gantry rotation) and at 16 cm depth for pelvis CBCT acquisition ( X ray beam energy used is 125 kV and 360 degree of gantry rotation) in specially designed phantom. We used farmer chamber which was calibrated inmore » kV X ray range for measurements .Dose was measured with default field size, and reducing field size along y direction to 10 cm and 5 cm. Results: As the energy of the beam decreases the scattered radiation increases and this contributes significantly to the dose deposited in the patient. By reducing the scan length to 10 Cm from default 20.6 cm we found a dose reduction of 14% for head and neck CBCT protocol and a reduction of 26% for pelvis CBCT protocol. Similarly for a scan length of 5cm compared to default the dose reduction in head and neck CBCT protocol is 36% while in the pelvis CBCT protocol the dose reduction is 50%. Conclusion: By limiting the scan length we can control the scatter radiation generated and hence the dose to the patient. However the variation in dose reduction for same length used in two protocols is because of the scan geometry. The pelvis CBCT protocol uses a full rotation and head and neck CBCT protocol uses partial rotation.« less

Evaluating the effect of increased pitch, iterative reconstruction and dual source CT on dose reduction and image quality.

PubMed

Gariani, Joanna; Martin, Steve P; Botsikas, Diomidis; Becker, Christoph D; Montet, Xavier

2018-06-14

To compare radiation dose and image quality of thoracoabdominal scans obtained with a high-pitch protocol (pitch 3.2) and iterative reconstruction (Sinogram Affirmed Iterative Reconstruction) in comparison to standard pitch reconstructed with filtered back projection (FBP) using dual source CT. 114 CT scans (Somatom Definition Flash, Siemens Healthineers, Erlangen, Germany), 39 thoracic scans, 54 thoracoabdominal scans and 21 abdominal scans were performed. Analysis of three protocols was undertaken; pitch of 1 reconstructed with FBP, pitch of 3.2 reconstructed with SAFIRE, pitch of 3.2 with stellar detectors reconstructed with SAFIRE. Objective and subjective image analysis were performed. Dose differences of the protocols used were compared. Dose was reduced when comparing scans with a pitch of 1 reconstructed with FBP to high-pitch scans with a pitch of 3.2 reconstructed with SAFIRE with a reduction of volume CT dose index of 75% for thoracic scans, 64% for thoracoabdominal scans and 67% for abdominal scans. There was a further reduction after the implementation of stellar detectors reflected in a reduction of 36% of the dose-length product for thoracic scans. This was not at the detriment of image quality, contrast-to-noise ratio, signal-to-noise ratio and the qualitative image analysis revealed a superior image quality in the high-pitch protocols. The combination of a high pitch protocol with iterative reconstruction allows significant dose reduction in routine chest and abdominal scans whilst maintaining or improving diagnostic image quality, with a further reduction in thoracic scans with stellar detectors. Advances in knowledge: High pitch imaging with iterative reconstruction is a tool that can be used to reduce dose without sacrificing image quality.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

PubMed

Hirano, Emi; Fuji, Hiroshi; Onoe, Tsuyoshi; Kumar, Vinay; Shirato, Hiroki; Kawabuchi, Koichi

2014-03-01

The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Earlier therapeutic effects associated with high dose (2.0 mg) Ranibizumab for treatment of vascularized pigment epithelial detachments in age-related macular degeneration

PubMed Central

Chan, C K; Abraham, P; Sarraf, D; Nuthi, A S D; Lin, S G; McCannel, C A

2015-01-01

Summary statement Intravitreal high dose (2 mg) ranibizumab may lead to quicker resolution of choroidal neovascularization (CNV) and associated retinal pigment epithelial detachment in eyes with exudative age-related macular degeneration, although it may possibly correlate with RPE tears in certain cases. Purpose This prospective study compared the outcomes of 0.5 vs 2.0 mg intravitreal ranibizumab injections (RI) for treating vascularized pigment epithelial detachment (vPED) due to age-related macular degeneration. Methods Patients with vPED were randomized to receive 2.0 vs 0.5 mg RI monthly for 12 months or for 4 months and then repeated on a pro-re nata basis. Optical coherence tomography, fundus photography, and fluorescein and indocyanine-green angiography were obtained at baseline and subsequent specific intervals. Outcome measures were best-corrected standardized visual acuities, central 1-mm thickness, surface area (SA), greatest linear diameter (GLD), heights (PED and CNV), and amount of subretinal fluid (SRF) and cystoid macular edema (CME). Results Both groups yielded reductions of the central 1-mm thickness, PED and CNV SA and PED height and GLD, SRF, and CME. Vision improvement and reduction in SRF and PED height occurred earlier for eyes receiving the 2.0 mg dose. Cataract progression was similar but RPE tears developed more often with the 2.0 mg dose. Conclusions There were similar visual and anatomical outcomes at the end of the study; however, the higher dose yielded more rapid reductions and more complete resolution of the PED, although there was possible increased tendency for an RPE tear with the higher dose. PMID:25277305

Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter.

PubMed

Nieuwlaat, Willy-Anne; Huysmans, Dyde A; van den Bosch, Harrie C; Sweep, C G Fred; Ross, H Alec; Corstens, Frans H; Hermus, Ad R

2003-07-01

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.

Combined treatment using irradiation and heat: Susceptibility of bacillus, salmonella, staphylococcus and clostridium

NASA Astrophysics Data System (ADS)

Vincent, F.; Tibi, A.; Goury, V.; Darbord, J. C.

The development of irradiation for food preservation is dependant on good process for choosing the doses. The reduction of the doses is particularly suitable, not only for the cost, but for organoleptic qualities of food. Many studies have demonstrated that Bacillus, Salmonella, Staphylococcus and Clostridium species are frequently isolated from food. The objective of this work is to prove the efficiency of combined treatments using irradiation and temperature (80°C), to reduce the dose of irradiation and the organoleptic alterations of food. The results are dependant on environmental conditions of the bacteria.

Evaluation of the low dose cardiac CT imaging using ASIR technique

NASA Astrophysics Data System (ADS)

Fan, Jiahua; Hsieh, Jiang; Deubig, Amy; Sainath, Paavana; Crandall, Peter

2010-04-01

Today Cardiac imaging is one of the key driving forces for the research and development activities of Computed Tomography (CT) imaging. It requires high spatial and temporal resolution and is often associated with high radiation dose. The newly introduced ASIR technique presents an efficient method that offers the dose reduction benefits while maintaining image quality and providing fast reconstruction speed. This paper discusses the study of image quality of the ASIR technique for Cardiac CT imaging. Phantoms as well as clinical data have been evaluated to demonstrate the effectiveness of ASIR technique for Cardiac CT applications.

Chronic Exposure to Low Doses of HgCl2 Avoids Calcium Handling Impairment in the Right Ventricle after Myocardial Infarction in Rats

PubMed Central

Faria, Thaís de Oliveira; Costa, Gustavo Pinto; Almenara, Camila Cruz Pereira; Angeli, Jhuli Keli; Vassallo, Dalton Valentim; Stefanon, Ivanita; Vassallo, Paula Frizera

2014-01-01

Right ventricle systolic dysfunction is a major risk factor for death and heart failure after myocardial infarction (MI). Heavy metal exposure has been associated with the development of several cardiovascular diseases, such as MI. The aim of this study was to investigate whether chronic exposure to low doses of mercury chloride (HgCl2) enhances the functional deterioration of right ventricle strips after MI. Male Wistar rats were divided into four groups: Control (vehicle); HgCl2 (exposure during 4 weeks- 1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, i.m. to cover daily loss); MI surgery induced and HgCl2-MI groups. One week after MI, the morphological and hemodynamic measurements and isometric tension of right ventricle strips were investigated. The chronic HgCl2 exposure did not worsen the injury compared with MI alone in the morphological or hemodynamic parameters evaluated. At basal conditions, despite similar maximum isometric force at L-max, relaxation time was increased in the MI group but unaffected in the HgCl2-MI compared to the Control group. Impairment of the sarcoplasmic reticulum (SR) function and reduction in the sarcolemmal calcium influx were observed in MI group associated with SERCA2a reduction and increased PLB protein expression. Induction of MI in chronic HgCl2 exposed rats did not cause any alteration in the developed force at L-max, lusitropic function or −dF/dt except for a tendency of a reduction SR function. These findings could be partially explained by the normalization in the sarcolemmal calcium influx and the increase in NCX protein expression observed only in this group. These results suggest that chronic exposure to low doses of HgCl2 prevents the impaired SR function and the reduced sarcolemmal calcium influx observed in MI likely by acting on NCX, PLB and SERCA2a protein expression. PMID:24748367

Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

PubMed

Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

2011-01-01

The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of <3% and estimate the remaining medication volume with an accuracy of >98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: a one-week clinical confinement study.

PubMed

Theophilus, Eugenia H; Coggins, Christopher R E; Chen, Peter; Schmidt, Eckhardt; Borgerding, Michael F

2015-03-01

Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-J-07: IGRT Gently: Evaluating Imaging Dose in Phantoms of Different Sizes

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

Morris, B; Duggar, W; Stanford, J

Purpose: IGRT imaging procedures have emerged as a common method of patient position verification in radiotherapy, though imaging dose is generally neglected in the treatment plan. Consequently, evaluating and optimizing the dose from these procedures is worthwhile. This process is especially important for children, who are more radiosensitive than adults. The aim of this work was to gain some understanding of the relative doses involved with various XVI-preset parameters for an “adult” and “child” phantom set, with the hopes that imaging dose for a child can be reduced. Methods: 32 and 16cm CTDI-phantoms were used as surrogates for adult andmore » child torsos, respectively. Dose was measured in the central and peripheral chamber positions of the phantoms. CBCT scans were made for both phantoms using Elekta’s Chest-preset to establish a dose baseline. The child-phantom was then scanned using the Elekta Head and Neck (HN) preset. A modified HN-preset (named Peds Abd-pelvis) was also created with a doubled mAs to maintain a reduction in dose to the child-phantom (relative to the baseline), while providing clinically-usable image quality. Results: The baseline dose to the child-phantom from the Chest-preset was 310% that of the adult-phantom for the center chamber position and 150% at the periphery. An average dose reduction of 97% was obtained in the childphantom by switching from the Chest-preset to the HN-preset, while the Peds Abd-pelvis-preset similarly reduced the dose by an average of 92%. Conclusion: XVI-preset parameters significantly affect dose, and should be optimized to reduce dose, while ensuring clinically-usable image quality. Using a modified imaging preset (Peds Abd-pelvis-preset) greatly reduced the dose to the child-phantom compared to the dose for the Chest-preset for both the child and adult-phantoms. This outcome provides support for the development of child-specific protocols for IGRT imaging in pediatric patients.« less

Efficacy of a radiation absorbing shield in reducing dose to the interventionalist during peripheral endovascular procedures: a single centre pilot study.

PubMed

Power, S; Mirza, M; Thakorlal, A; Ganai, B; Gavagan, L D; Given, M F; Lee, M J

2015-06-01

This prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures. A commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated. TLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142). Initial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator's body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

2014-03-01

We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

Volume of interest CBCT and tube current modulation for image guidance using dynamic kV collimation

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

Parsons, David, E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca; Robar, James L., E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca

2016-04-15

Purpose: The focus of this work is the development of a novel blade collimation system enabling volume of interest (VOI) CBCT with tube current modulation using the kV image guidance source on a linear accelerator. Advantages of the system are assessed, particularly with regard to reduction and localization of dose and improvement of image quality. Methods: A four blade dynamic kV collimator was developed to track a VOI during a CBCT acquisition. The current prototype is capable of tracking an arbitrary volume defined by the treatment planner for subsequent CBCT guidance. During gantry rotation, the collimator tracks the VOI withmore » adjustment of position and dimension. CBCT image quality was investigated as a function of collimator dimension, while maintaining the same dose to the VOI, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert centered on isocenter. Dose distributions were modeled using a dynamic BEAMnrc library and DOSXYZnrc. The resulting VOI dose distributions were compared to full-field CBCT distributions to quantify dose reduction and localization to the target volume. A novel method of optimizing x-ray tube current during CBCT acquisition was developed and assessed with regard to contrast-to-noise ratio (CNR) and imaging dose. Results: Measurements show that the VOI CBCT method using the dynamic blade system yields an increase in contrast-to-noise ratio by a factor of approximately 2.2. Depending upon the anatomical site, dose was reduced to 15%–80% of the full-field CBCT value along the central axis plane and down to less than 1% out of plane. The use of tube current modulation allowed for specification of a desired SNR within projection data. For approximately the same dose to the VOI, CNR was further increased by a factor of 1.2 for modulated VOI CBCT, giving a combined improvement of 2.6 compared to full-field CBCT. Conclusions: The present dynamic blade system provides significant improvements in CNR for the same imaging dose and localization of imaging dose to a predefined volume of interest. The approach is compatible with tube current modulation, allowing optimization of the imaging protocol.« less

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

PubMed

Craven, Meghan; Frank, Graeme R

2018-06-27

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. This study is a retrospective chart review of infants with CH between 2002 and 2012. Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007). Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

Clinical implementation of a knowledge based planning tool for prostate VMAT.

PubMed

Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth

2017-05-08

A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression.

PubMed

Bisi, John E; Sorrentino, Jessica A; Roberts, Patrick J; Tavares, Francis X; Strum, Jay C

2016-05-01

Chemotherapy-induced myelosuppression continues to represent the major dose-limiting toxicity of cytotoxic chemotherapy, which can be manifested as neutropenia, lymphopenia, anemia, and thrombocytopenia. As such, myelosuppression is the source of many of the adverse side effects of cancer treatment including infection, sepsis, bleeding, and fatigue, thus resulting in the need for hospitalizations, hematopoietic growth factor support, and transfusions (red blood cells and/or platelets). Moreover, clinical concerns raised by myelosuppression commonly lead to chemotherapy dose reductions, therefore limiting therapeutic dose intensity, and reducing the antitumor effectiveness of the treatment. Currently, the only course of treatment for myelosuppression is growth factor support which is suboptimal. These treatments are lineage specific, do not protect the bone marrow from the chemotherapy-inducing cytotoxic effects, and the safety and toxicity of each agent is extremely specific. Here, we describe the preclinical development of G1T28, a novel potent and selective CDK4/6 inhibitor that transiently and reversibly regulates the proliferation of murine and canine bone marrow hematopoietic stem and progenitor cells and provides multilineage protection from the hematologic toxicity of chemotherapy. Furthermore, G1T28 does not decrease the efficacy of cytotoxic chemotherapy on RB1-deficient tumors. G1T28 is currently in clinical development for the reduction of chemotherapy-induced myelosuppression in first- and second-line treatment of small-cell lung cancer. Mol Cancer Ther; 15(5); 783-93. ©2016 AACR. ©2016 American Association for Cancer Research.

Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

PubMed

Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

2017-06-01

Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?

PubMed

Tschakovsky, Michael E; Sujirattanawimol, Kittiphong; Ruble, Stephen B; Valic, Zoran; Joyner, Michael J

2002-06-01

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n = 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n = 7) and two doses of sodium nitroprusside (SNP) infusion (n = 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non-invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose-dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42-46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest -43.4 +/- 3.7 %, moderate exercise -27.5 +/- 2.3 %, heavy exercise -16.7 +/- 3.6 %; P < 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosine vs. rest (P < 0.05). Finally, percentage change in FVC was greater during low dose SNP infusion vs. rest (P < 0.05), but not different from rest at the high dose of SNP infusion (P = 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity-dependent.

Effects of low-dose γ-rays on the embryonic development of mouse melanoblasts and melanocytes in the epidermis and hair bulbs.

PubMed

Hirobe, Tomohisa; Eguchi-Kasai, Kiyomi; Sugaya, Kimihiko; Murakami, Masahiro

2011-06-01

The effects of low-dose γ-rays on the embryonic development of animal cells are not well studied. The mouse melanocyte is a good model to study the effects of low-dose γ-rays on the development of animal cells, as it possesses visible pigment (melanin) as a differentiation marker. The aim of this study is to investigate in detail the effects of low-dose γ-rays on embryonic development of mouse melanoblasts and melanocytes in the epidermis and hair bulbs at cellular level. Pregnant females of C57BL/10J mice at nine days of gestation were whole-body irradiated with a single acute dose of γrays (0.1, 0.25, 0.5, and 0.75 Gy), and the effects of γ-rays were studied by scoring changes in the development of epidermal melanoblasts and melanocytes, hair follicles, and hair bulb melanocytes at 18 days in gestation. The number of epidermal melanoblasts and melanocytes, hair follicles, and hair bulb melanocytes in the dorsal and ventral skins was markedly decreased even at 0.1 Gy-treated embryos (P < 0.001), and gradually decreased as dose increased. The effects on the ventral skin were greater than those on the dorsal skin. The dramatic reduction in the number of melanocytes compared to melanoblasts was observed in the ventral skin, but not in the dorsal skin. These results suggest that low-dose γ-rays provoke the death of melanoblasts and melanocytes, or inhibit the proliferation and differentiation of melanoblasts and melanocytes, even at the low dose.

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment;HDR; Uterine cervix cancer; Vaginal balloon packing; Contrast; Monte Carlo

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

Saini, Amarjit S.; Zhang, Geoffrey G., E-mail: geoffrey.zhang@moffitt.org; Finkelstein, Steven E.

2011-07-15

Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken withmore » each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 {+-} 0.002 for contrast/saline solution and 0.808 {+-} 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 {+-} 0.010 and 0.781 {+-} 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.« less

Pediatric cT: Implementation of ASIR for Substantial Radiation Dose Reduction While Maintaining Pre-ASIR Image Noise1

PubMed Central

Brady, Samuel L.; Moore, Bria M.; Yee, Brian S.; Kaufman, Robert A.

2015-01-01

Purpose To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. Materials and Methods The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current–modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. Results With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Conclusion Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. PMID:23901128

Ultralow Dose MSCT Imaging in Dental Implantology

PubMed Central

Widmann, Gerlig; Al-Ekrish, Asma'a A.

2018-01-01

Introduction: The Council Directive 2013/59 Euratom has a clear commitment for keeping medical radiation exposure as low as reasonably achievable and demands a regular review and use of diagnostic reference levels. Methods: In dental implantology, the range of effective doses for cone beam computed tomography (CBCT) shows a broad overlap with multislice computed tomography (MSCT). More recently, ultralow dose imaging with new generations of MSCT scanners may impart radiation doses equal to or lower than CBCT. Dose reductions in MSCT have been further facilitated by the introduction of iterative image reconstruction technology (IRT), which provides substantial noise reduction over the current standard of filtered backward projection (FBP). Aim: The aim of this article is to review the available literature on ultralow dose CT imaging and IRTs in dental implantology imaging and to summarize their influence on spatial and contrast resolution, image noise, tissue density measurements, and validity of linear measurements of the jaws. Conclusion: Application of ultralow dose MSCT with IRT technology in dental implantology offers the potential for very large dose reductions compared with standard dose imaging. Yet, evaluation of various diagnostic tasks related to dental implantology is still needed to confirm the results obtained with various IRTs and ultra-low doses so far. PMID:29492174

Does the choice of mobile C-arms lead to a reduction of the intraoperative radiation dose?

PubMed

Richter, P H; Steinbrener, J; Schicho, A; Gebhard, F

2016-08-01

Mobile C-arm imaging is commonly used in operating rooms worldwide. Especially in orthopaedic surgery, intraoperative C-arms are used on a daily basis. Because of new minimally-invasive surgical procedures a development in intraoperative imaging is required. The purpose of this article is investigate if the choice of mobile C-arms with flat panel detector technology (Siemens Cios Alpha and Ziehm Vision RFD) influences image quality and dose using standard, commercially available test devices. For a total of four clinical application settings, two zoom formats, and all dose levels provided, the transmission dose was measured and representative images were recorded for each test device. The data was scored by four observers to assess low contrast and spatial resolution performance. The results were converted to a relative image quality figure allowing for a direct image quality and dose comparison of the two systems. For one test device, the Cios Alpha system achieved equivalent (within the inter-observer standard error) or better low contrast resolution scores at significantly lower dose levels, while the results of the other test device suggested that both systems achieved similar image quality at the same dose. The Cios Alpha system achieved equivalent or better spatial resolution at significantly lower dose for all application settings except for Cardiac, where a comparable spatial resolution was achieved at the same dose. The correct choice of a mobile C-arm is very important, because it can lead to a reduction of the intraoperative radiation dose without negative effects on image quality. This can be a big advantage to reduce intraoperative radiation not only for the patient but also for the entire OR-team. Copyright © 2016. Published by Elsevier Ltd.

Monte Carlo investigation of backscatter point spread function for x-ray imaging examinations

NASA Astrophysics Data System (ADS)

Xiong, Zhenyu; Vijayan, Sarath; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.

PubMed

Troy, Stephanie B; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

2015-06-15

Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS.

PubMed

Schüler, Emil; Eriksson, Kjell; Hynning, Elin; Hancock, Steven L; Hiniker, Susan M; Bazalova-Carter, Magdalena; Wong, Tony; Le, Quynh-Thu; Loo, Billy W; Maxim, Peter G

2017-06-01

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization. Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques. The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200 MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan. The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing. © 2017 American Association of Physicists in Medicine.

Measles control strategies in India: position paper of Indian Academy of Pediatrics.

PubMed

Vashishtha, V M; Choudhury, P; Bansal, C P; Gupta, S G

2013-06-08

Measles continues to be a major cause of childhood morbidity and mortality in India. Recent studies estimate that 80,000 Indian children die each year due to measles and its complications, amounting to 4% of under-5 deaths. Immunization against measles directly contributes to the reduction of under five child mortality and hence to the achievement of Millennium Development Goal 4 (MDG 4). The live attenuated measles vaccines are safe, effective and provide long lasting protection. The key strategies being followed globally for measles mortality reduction are high coverage of measles first dose, sensitive laboratory supported surveillance, appropriate case management, and providing second dose of measles vaccine. Prior to 2010, India was the only country in the world that had not introduced a second dose of measles vaccine in its National immunization program. We herein discuss the current status of measles vaccination along with the rationale and challenges of providing a second opportunity for measles vaccination, and the principles of measles catch-up campaigns.

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.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

PubMed

Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

2016-02-25

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

Diagnostic accuracy of 256-row multidetector CT coronary angiography with prospective ECG-gating combined with fourth-generation iterative reconstruction algorithm in the assessment of coronary artery bypass: evaluation of dose reduction and image quality.

PubMed

Ippolito, Davide; Fior, Davide; Franzesi, Cammillo Talei; Riva, Luca; Casiraghi, Alessandra; Sironi, Sandro

2017-12-01

Effective radiation dose in coronary CT angiography (CTCA) for coronary artery bypass graft (CABG) evaluation is remarkably high because of long scan lengths. Prospective electrocardiographic gating with iterative reconstruction can reduce effective radiation dose. To evaluate the diagnostic performance of low-kV CT angiography protocol with prospective ecg-gating technique and iterative reconstruction (IR) algorithm in follow-up of CABG patients compared with standard retrospective protocol. Seventy-four non-obese patients with known coronary disease treated with artery bypass grafting were prospectively enrolled. All the patients underwent 256 MDCT (Brilliance iCT, Philips) CTCA using low-dose protocol (100 kV; 800 mAs; rotation time: 0.275 s) combined with prospective ECG-triggering acquisition and fourth-generation IR technique (iDose 4 ; Philips); all the lengths of the bypass graft were included in the evaluation. A control group of 42 similar patients was evaluated with a standard retrospective ECG-gated CTCA (100 kV; 800 mAs).On both CT examinations, ROIs were placed to calculate standard deviation of pixel values and intra-vessel density. Diagnostic quality was also evaluated using a 4-point quality scale. Despite the statistically significant reduction of radiation dose evaluated with DLP (study group mean DLP: 274 mGy cm; control group mean DLP: 1224 mGy cm; P value < 0.001). No statistical differences were found between PGA group and RGH group regarding intra-vessel density absolute values and SNR. Qualitative analysis, evaluated by two radiologists in "double blind", did not reveal any significant difference in diagnostic quality of the two groups. The development of high-speed MDCT scans combined with modern IR allows an accurate evaluation of CABG with prospective ECG-gating protocols in a single breath hold, obtaining a significant reduction in radiation dose.

SU-E-I-37: Low-Dose Real-Time Region-Of-Interest X-Ray Fluoroscopic Imaging with a GPU-Accelerated Spatially Different Bilateral Filtering

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

Chung, H; Lee, J; Pua, R

2014-06-01

Purpose: The purpose of our study is to reduce imaging radiation dose while maintaining image quality of region of interest (ROI) in X-ray fluoroscopy. A low-dose real-time ROI fluoroscopic imaging technique which includes graphics-processing-unit- (GPU-) accelerated image processing for brightness compensation and noise filtering was developed in this study. Methods: In our ROI fluoroscopic imaging, a copper filter is placed in front of the X-ray tube. The filter contains a round aperture to reduce radiation dose to outside of the aperture. To equalize the brightness difference between inner and outer ROI regions, brightness compensation was performed by use of amore » simple weighting method that applies selectively to the inner ROI, the outer ROI, and the boundary zone. A bilateral filtering was applied to the images to reduce relatively high noise in the outer ROI images. To speed up the calculation of our technique for real-time application, the GPU-acceleration was applied to the image processing algorithm. We performed a dosimetric measurement using an ion-chamber dosimeter to evaluate the amount of radiation dose reduction. The reduction of calculation time compared to a CPU-only computation was also measured, and the assessment of image quality in terms of image noise and spatial resolution was conducted. Results: More than 80% of dose was reduced by use of the ROI filter. The reduction rate depended on the thickness of the filter and the size of ROI aperture. The image noise outside the ROI was remarkably reduced by the bilateral filtering technique. The computation time for processing each frame image was reduced from 3.43 seconds with single CPU to 9.85 milliseconds with GPU-acceleration. Conclusion: The proposed technique for X-ray fluoroscopy can substantially reduce imaging radiation dose to the patient while maintaining image quality particularly in the ROI region in real-time.« less

Development of a Chlorine Dosing Strategy for Fresh Produce Washing Process to Maintain Microbial Food Safety and Minimize Residual Chlorine.

PubMed

Chen, Xi; Hung, Yen-Con

2018-06-01

The residual free chlorine level in fresh produce wash solution is closely correlated to the chemical and microbial safety of produce. Excess amount of free chlorine can quickly react with organic matters to form hazardous disinfection by-products (DBPs) above EPA-permitted levels, whereas deficiency of residual chlorine in produce wash solution may result in incompletely removing pathogens on produce. The purpose of this study was to develop a chlorine dosing strategy to optimize the chlorine dosage during produce washing process without impacting the microbial safety of fresh produce. Prediction equations were developed to estimate free chlorine needed to reach targeted residual chlorine at various sanitizer pH and organic loads, and then validated using fresh-cut iceberg lettuce and whole strawberries in an automated produce washer. Validation results showed that equations successfully predicted the initial chlorine concentration needed to achieve residual chlorine at 10, 30, 60, and 90 mg/L for both lettuce and strawberry washing processes, with the root mean squared error at 4.45 mg/L. The Escherichia coli O157:H7 reductions only slightly increased on iceberg lettuce and strawberries with residual chlorine increasing from 10 to 90 mg/L, indicating that lowering residual chlorine to 10 mg/L would not compromise the antimicrobial efficacy of chlorine-based sanitizer. Based on the prediction equations and E. coli O157:H7 reduction results, a chlorine dosing strategy was developed to help the produce industry to maintain microbial inactivation efficacy without adding excess amount of free chlorine. The chlorine dosing strategy can be used for fresh produce washing process to enhance the microbial food safety and minimize the DBPs formation potential. © 2018 Institute of Food Technologists®.

SU-G-IeP3-05: Effects of Image Receptor Technology and Dose Reduction Software On Radiation Dose Estimates for Fluoroscopically-Guided Interventional (FGI) Procedures

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

Merritt, Z; Dave, J; Eschelman, D

Purpose: To investigate the effects of image receptor technology and dose reduction software on radiation dose estimates for most frequently performed fluoroscopically-guided interventional (FGI) procedures at a tertiary health care center. Methods: IRB approval was obtained for retrospective analysis of FGI procedures performed in the interventional radiology suites between January-2011 and December-2015. This included procedures performed using image-intensifier (II) based systems which were subsequently replaced, flat-panel-detector (FPD) based systems which were later upgraded with ClarityIQ dose reduction software (Philips Healthcare) and relatively new FPD system already equipped with ClarityIQ. Post procedure, technologists entered system-reported cumulative air kerma (CAK) and kerma-areamore » product (KAP; only KAP for II based systems) in RIS; these values were analyzed. Data pre-processing included correcting typographical errors and cross-verifying CAK and KAP. The most frequent high and low dose FGI procedures were identified and corresponding CAK and KAP values were compared. Results: Out of 27,251 procedures within this time period, most frequent high and low dose procedures were chemo/immuno-embolization (n=1967) and abscess drainage (n=1821). Mean KAP for embolization and abscess drainage procedures were 260,657, 310,304 and 94,908 mGycm{sup 2}, and 14,497, 15,040 and 6307 mGycm{sup 2} using II-, FPD- and FPD with ClarityIQ- based systems, respectively. Statistically significant differences were observed in KAP values for embolization procedures with respect to different systems but for abscess drainage procedures significant differences were only noted between systems with FPD and FPD with ClarityIQ (p<0.05). Mean CAK reduced significantly from 823 to 308 mGy and from 43 to 21 mGy for embolization and abscess drainage procedures, respectively, in transitioning to FPD systems with ClarityIQ (p<0.05). Conclusion: While transitioning from II- to FPD- based systems was not associated with dose reduction for the most frequently performed FGI procedures, substantial dose reduction was noted with relatively newer systems and dose reduction software.« less

A Novel Pairwise Comparison-Based Method to Determine Radiation Dose Reduction Potentials of Iterative Reconstruction Algorithms, Exemplified Through Circle of Willis Computed Tomography Angiography.

PubMed

Ellmann, Stephan; Kammerer, Ferdinand; Brand, Michael; Allmendinger, Thomas; May, Matthias S; Uder, Michael; Lell, Michael M; Kramer, Manuel

2016-05-01

The aim of this study was to determine the dose reduction potential of iterative reconstruction (IR) algorithms in computed tomography angiography (CTA) of the circle of Willis using a novel method of evaluating the quality of radiation dose-reduced images. This study relied on ReconCT, a proprietary reconstruction software that allows simulating CT scans acquired with reduced radiation dose based on the raw data of true scans. To evaluate the performance of ReconCT in this regard, a phantom study was performed to compare the image noise of true and simulated scans within simulated vessels of a head phantom. That followed, 10 patients scheduled for CTA of the circle of Willis were scanned according to our institute's standard protocol (100 kV, 145 reference mAs). Subsequently, CTA images of these patients were reconstructed as either a full-dose weighted filtered back projection or with radiation dose reductions down to 10% of the full-dose level and Sinogram-Affirmed Iterative Reconstruction (SAFIRE) with either strength 3 or 5. Images were marked with arrows pointing on vessels of different sizes, and image pairs were presented to observers. Five readers assessed image quality with 2-alternative forced choice comparisons. In the phantom study, no significant differences were observed between the noise levels of simulated and true scans in filtered back projection, SAFIRE 3, and SAFIRE 5 reconstructions.The dose reduction potential for patient scans showed a strong dependence on IR strength as well as on the size of the vessel of interest. Thus, the potential radiation dose reductions ranged from 84.4% for the evaluation of great vessels reconstructed with SAFIRE 5 to 40.9% for the evaluation of small vessels reconstructed with SAFIRE 3. This study provides a novel image quality evaluation method based on 2-alternative forced choice comparisons. In CTA of the circle of Willis, higher IR strengths and greater vessel sizes allowed higher degrees of radiation dose reduction.

Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes

PubMed Central

Rosada, Rogério S; Torre, Lucimara Gaziola de la; Frantz, Fabiani G; Trombone, Ana PF; Zárate-Bladés, Carlos R; Fonseca, Denise M; Souza, Patrícia RM; Brandão, Izaíra T; Masson, Ana P; Soares, Édson G; Ramos, Simone G; Faccioli, Lúcia H; Silva, Célio L; Santana, Maria HA; Coelho-Castelo, Arlete AM

2008-01-01

Background The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally. Results We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg). Conclusion Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease. PMID:18647414

Eye lens radiation exposure to interventional cardiologists: a retrospective assessment of cumulative doses.

PubMed

Jacob, Sophie; Donadille, Laurent; Maccia, Carlo; Bar, Olivier; Boveda, Serge; Laurier, Dominique; Bernier, Marie-Odile

2013-03-01

Radiation dose to the eye lens is a crucial issue for interventional cardiologists (ICs) who are exposed during the procedures they perform. This paper presents a retrospective assessment of the cumulative eye lens doses of ICs enrolled in the O'CLOC study for Occupational Cataracts and Lens Opacities in interventional Cardiology. Information on the workload in the catheterisation laboratory, radiation protection equipment, eye lens dose per procedure and dose reduction factors associated with eye-protective equipment were considered. For the 129 ICs at an average age of 51 who had worked for an average period of 22 years, the estimated cumulative eye lens dose ranged from 25 mSv to more than 1600 mSv; the mean ± SD was 423 ± 359 mSv. After several years of practice, without eye protection, ICs may exceed the new ICRP lifetime eye dose threshold of 500 mSv and be at high risk of developing early radiation-induced cataracts. Radiation protection equipment can reduce these doses and should be used routinely.

Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

PubMed

Leonetti, G; Gradnik, R; Terzoli, L; Fruscio, M; Rupoli, L; Cuspidi, C; Sampieri, L; Zanchetti, A

1986-01-01

Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

Quantitative Analysis of the Effect of Iterative Reconstruction Using a Phantom: Determining the Appropriate Blending Percentage

PubMed Central

Kim, Hyun Gi; Lee, Young Han; Choi, Jin-Young; Park, Mi-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2015-01-01

Purpose To investigate the optimal blending percentage of adaptive statistical iterative reconstruction (ASIR) in a reduced radiation dose while preserving a degree of image quality and texture that is similar to that of standard-dose computed tomography (CT). Materials and Methods The CT performance phantom was scanned with standard and dose reduction protocols including reduced mAs or kVp. Image quality parameters including noise, spatial, and low-contrast resolution, as well as image texture, were quantitatively evaluated after applying various blending percentages of ASIR. The optimal blending percentage of ASIR that preserved image quality and texture compared to standard dose CT was investigated in each radiation dose reduction protocol. Results As the percentage of ASIR increased, noise and spatial-resolution decreased, whereas low-contrast resolution increased. In the texture analysis, an increasing percentage of ASIR resulted in an increase of angular second moment, inverse difference moment, and correlation and in a decrease of contrast and entropy. The 20% and 40% dose reduction protocols with 20% and 40% ASIR blending, respectively, resulted in an optimal quality of images with preservation of the image texture. Conclusion Blending the 40% ASIR to the 40% reduced tube-current product can maximize radiation dose reduction and preserve adequate image quality and texture. PMID:25510772

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective.

PubMed

Wehler, Thomas C; Graf, Claudine; Möhler, Markus; Herzog, Jutta; Berger, Martin R; Gockel, Ines; Lang, Hauke; Theobald, Matthias; Galle, Peter R; Schimanski, Carl C

2013-10-01

Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9-19 % of patients with the necessity of cetuximab dose reduction or cessation. The study presented was a retrospective analysis of 50 gastrointestinal cancer patients treated with cetuximab in combination with either FOLFIRI or FOLFOX. One cohort of 15 patients received an in-house reactive skin protocol upon development of an exanthema. A second cohort of 15 patients received a skin prophylaxis starting with the first dose of cetuximab before clinical signs of toxicity. A third historic group of 20 patients had received no skin prophylaxis or reactive treatment. 19/20 patients of the historic group developed a skin exanthema. Grade III/IV exanthema was observed six times. Forty percent discontinued cetuximab therapy. The average time to exanthema onset was 14.7 days. Applying the reactive skin protocol after the first occurrence of an exanthema, the exanthema was downgraded as follows: No patients developed grade IV° exanthema, and two patients developed a grade II/III exanthema. In the majority of cases, the reactive skin protocol controlled the exanthema (grade 0-I°). No dose reductions in cetuximab were necessary. Applying the prophylactic skin protocol starting at the beginning of cetuximab application was not superior to the reactive skin protocol. Cetuximab-induced skin exanthema can be coped with a reactive protocol equally effective as compared to a prophylactic skin treatment. A prospective study with higher patient numbers is planned.

Surface dose measurements from air gaps under a bolus by using a MOSFET dosimeter in clinical oblique photon beams

NASA Astrophysics Data System (ADS)

Chung, Jin-Beom; Kim, Jae-Sung; Kim, In-Ah; Lee, Jeong-Woo

2012-10-01

This study is intended to investigate the effects of surface dose from air gaps under the bolus in clinically used oblique photon beams by using a Markus parallel-plate chamber and a metal-oxide semiconductor field-effect transistor (MOSFET) dosimeter. To evaluate the performances of the two detectors, the percentage surface doses of the MOSFET dosimeters in without an air gap under the bolus material were measured and compared with those of the Markus parallel-plate chamber. MOSFET dosimeters at the surface provided results mostly in good agreement with the parallelplate chamber. The MOSFET dosimeters seemed suitable for surface dose measurements having excellent accuracy for clinical used photon beams. The relative surface doses were measured with air gaps (2, 5, 10 mm) and without an air gap under 3 different bolus setups: (1) unbolused (no bolus), (2) 5-mm bolus, and (3) 10-mm bolus. The reductions in the surface dose substantially increased with small field size, thick bolus, and large air gap. The absolute difference in the reductions of the surface dose between the MOSFET dosimeter and the Markus parallel-plate chamber was less than 1.1%. Results at oblique angles of incidence showed larger reductions in surface dose with increasing angle of incidence. The largest reduction in surface dose was recorded for a 6 × 6 cm2 field at a 60° angle of incidence with an 10-mm air gap under a 10-mm bolus. When a 10-mm bolus was used, a reduction in the surface dose with an air gap of up to 10.5% could be achieved by varying the field size and the incident angle. Therefore, air gaps under the bolus should be avoided in radiotherapy treatment, especially for photon beam with highly oblique angles of incidence.

CT breast dose reduction with the use of breast positioning and organ-based tube current modulation.

PubMed

Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory M; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M; Kazerooni, Ella A; Samei, Ehsan

2017-02-01

This study aimed to investigate the breast dose reduction potential of a breast-positioning (BP) technique for thoracic CT examinations with organ-based tube current modulation (OTCM). This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray-tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDI vol were used to compare three CT protocols: attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCM BP ). On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCM BP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCM BP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCM BP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. In thoracic CT examinations, OTCM with a breast-positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts. © 2016 American Association of Physicists in Medicine.

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

Prospective Evaluation of Prior Image Constrained Compressed Sensing (PICCS) Algorithm in Abdominal CT: A comparison of reduced dose with standard dose imaging

PubMed Central

Lubner, Meghan G.; Pickhardt, Perry J.; Kim, David H.; Tang, Jie; Munoz del Rio, Alejandro; Chen, Guang-Hong

2014-01-01

Purpose To prospectively study CT dose reduction using the “prior image constrained compressed sensing” (PICCS) reconstruction technique. Methods Immediately following routine standard dose (SD) abdominal MDCT, 50 patients (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced-dose (RD) scan (targeted dose reduction, 70-90%). DLP, CTDIvol and SSDE were compared. Several reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series. SD images with FBP served as reference standard. Two blinded readers evaluated each series for subjective image quality and focal lesion detection. Results Mean DLP, CTDIvol, and SSDE for RD series was 140.3 mGy*cm (median 79.4), 3.7 mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy*cm (median 345.8), 12.9 mGy (median 7.9 mGy) and 14.6 mGy (median 10.1) for SD series, respectively. Mean effective patient diameter was 30.1 cm (median 30), which translates to a mean SSDE reduction of 72% (p<0.001). RD-PICCS image quality score was 2.8±0.5, improved over the RD-FBP (1.7±0.7) and RD-ASIR(1.9±0.8)(p<0.001), but lower than SD (3.5±0.5)(p<0.001). Readers detected 81% (184/228) of focal lesions on RD-PICCS series, versus 67% (153/228) and 65% (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2) and RD-ASIR (44.1) (p<0.001). Conclusion PICCS allows for marked dose reduction at abdominal CT with improved image quality and diagnostic performance over reduced-dose FBP and ASIR. Further study is needed to determine indication-specific dose reduction levels that preserve acceptable diagnostic accuracy relative to higher-dose protocols. PMID:24943136

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

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

Zhou, Rachel; Ng, Angela; Constine, Louis S.

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohortmore » and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.« less

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

PubMed

Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.

Comparative reduction of Norwalk virus, poliovirus type 1, F+ RNA coliphage MS2 and Escherichia coli in miniature soil columns.

PubMed

Meschke, J S; Sobsey, M D

2003-01-01

Norwalk-like viruses (NLVs) are important agents of waterborne illness and have been linked to several groundwater-related outbreaks. The presence of human enteric viruses, in particular the presence of NLVs, is difficult to detect in the environment. Consequently, surrogate organisms are typically used as indicators of viruses from faecal contamination. Whether traditional bacterial indicators are reliable indicators for viral pathogens remains uncertain. Few studies have directly compared mobility and reduction of bacterial indicators (e.g. coliforms, Escherichia coli) and other surrogate indicators (coliphages) with pathogenic human viruses in soil systems. In this study the mobility and comparative reduction of the prototype NLV, Norwalk Virus (NV), was compared to poliovirus 1 (PV1), a bacterial indicator (E coli, EC) and a viral indicator (coliphage MS2) through miniature soil columns. Replicate, 10 cm deep, miniature columns were prepared using three soils representing a range of soil textures (sand, organic muck, and clay). Columns were initially conditioned, then incubated at 10-14 degrees C, dosed twice weekly for 8 weeks with one column pore volume of virus-seeded groundwater per dose, followed by 8 weeks of dosing with one column pore volume per dose of unseeded, simulated rainwater. Columns were allowed to drain after each dosing until an effluent volume equivalent to an applied dose was collected. Column effluents and doses were assayed for all viruses and EC. Rapid mobility with minimal reduction was observed for all organisms in the sand. Similar reductions were observed in organic muck for most organisms but NV showed a greater reduction. No organisms were shown to pass through the clay columns. Elution of viruses, in particular PV1, from the columns was gradual. After cessation of microbe dosing, E. coli was less detectable than viruses in column effluents and, therefore, unreliable as a virus indicator.

Dose reduction in molecular breast imaging

NASA Astrophysics Data System (ADS)

Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

2011-10-01

Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

Influence of electron beam irradiation on growth of Phytophthora cinnamomi and its control in substrates

NASA Astrophysics Data System (ADS)

MigdaŁ, Wojciech; Orlikowski, Leszek B.; Ptaszek, Magdalena; Gryczka, Urszula

2012-08-01

Very extensive production procedure, especially in plants growing under covering, require methods, which would allow quick elimination or substantial reduction of populations of specific pathogens without affecting the growth and development of the cultivated plants. Among soil-borne pathogens, the Phytophthora species are especially dangerous for horticultural plants. In this study, irradiation with electron beam was applied to control Phytophthora cinnamomi. The influence of irradiation dose on the reduction of in vitro growth and the population density of the pathogen in treated peat and its mixture with composted pine bark (1:1), as well as the health of Chamaecyparis lawsoniana and Lavandula angustifolia plants were evaluated. Application of irradiation at a dose of 1.5 kGy completely inhibited the in vitro development of P. cinnamomi. This irradiation effect was connected with the disintegration of the hyphae and spores of the species. Irradiation of peat and its mixture with composted pine bark with 10 kGy resulted in the inhibition of stem base rot development in Ch. lawsoniana. Symptoms of the disease were not observed when the substrates were treated with 15 kGy. In the case of L. angustifolia, stem root rot was not observed on cuttings transplanted to infected peat irradiated at a dose of 10 kGy. Irradiation of the horticultural substrates did not affect plant growth.

The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

NASA Astrophysics Data System (ADS)

Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

2013-07-01

This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

Intussusception reduction: Effect of air vs. liquid enema on radiation dose.

PubMed

Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Edgar, J Christopher; Anupindi, Sudha A; Zhu, Xiaowei

2017-10-01

Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells. We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference. We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively. The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm 2 , than for liquid, 3.5 ± 2.5 dGy·cm 2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm 2 /min, than for liquid, 1.4 ± 0.5 dGy·cm 2 /min (P<0.001). No group differences were identified in other measured dose parameters. Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.

Characterization of adaptive statistical iterative reconstruction algorithm for dose reduction in CT: A pediatric oncology perspective

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

Brady, S. L.; Yee, B. S.; Kaufman, R. A.

Purpose: This study demonstrates a means of implementing an adaptive statistical iterative reconstruction (ASiR Trade-Mark-Sign ) technique for dose reduction in computed tomography (CT) while maintaining similar noise levels in the reconstructed image. The effects of image quality and noise texture were assessed at all implementation levels of ASiR Trade-Mark-Sign . Empirically derived dose reduction limits were established for ASiR Trade-Mark-Sign for imaging of the trunk for a pediatric oncology population ranging from 1 yr old through adolescence/adulthood. Methods: Image quality was assessed using metrics established by the American College of Radiology (ACR) CT accreditation program. Each image quality metricmore » was tested using the ACR CT phantom with 0%-100% ASiR Trade-Mark-Sign blended with filtered back projection (FBP) reconstructed images. Additionally, the noise power spectrum (NPS) was calculated for three common reconstruction filters of the trunk. The empirically derived limitations on ASiR Trade-Mark-Sign implementation for dose reduction were assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms. To assess dose reduction limits, the phantoms were scanned in increments of increased noise index (decrementing mA using automatic tube current modulation) balanced with ASiR Trade-Mark-Sign reconstruction to maintain noise equivalence of the 0% ASiR Trade-Mark-Sign image. Results: The ASiR Trade-Mark-Sign algorithm did not produce any unfavorable effects on image quality as assessed by ACR criteria. Conversely, low-contrast resolution was found to improve due to the reduction of noise in the reconstructed images. NPS calculations demonstrated that images with lower frequency noise had lower noise variance and coarser graininess at progressively higher percentages of ASiR Trade-Mark-Sign reconstruction; and in spite of the similar magnitudes of noise, the image reconstructed with 50% or more ASiR Trade-Mark-Sign presented a more smoothed appearance than the pre-ASiR Trade-Mark-Sign 100% FBP image. Finally, relative to non-ASiR Trade-Mark-Sign images with 100% of standard dose across the pediatric phantom age spectrum, similar noise levels were obtained in the images at a dose reduction of 48% with 40% ASIR Trade-Mark-Sign and a dose reduction of 82% with 100% ASIR Trade-Mark-Sign . Conclusions: The authors' work was conducted to identify the dose reduction limits of ASiR Trade-Mark-Sign for a pediatric oncology population using automatic tube current modulation. Improvements in noise levels from ASiR Trade-Mark-Sign reconstruction were adapted to provide lower radiation exposure (i.e., lower mA) instead of improved image quality. We have demonstrated for the image quality standards required at our institution, a maximum dose reduction of 82% can be achieved using 100% ASiR Trade-Mark-Sign ; however, to negate changes in the appearance of reconstructed images using ASiR Trade-Mark-Sign with a medium to low frequency noise preserving reconstruction filter (i.e., standard), 40% ASiR Trade-Mark-Sign was implemented in our clinic for 42%-48% dose reduction at all pediatric ages without a visually perceptible change in image quality or image noise.« less

Potential of combining iterative reconstruction with noise efficient detector design: aggressive dose reduction in head CT

PubMed Central

Bender, B; Schabel, C; Fenchel, M; Ernemann, U; Korn, A

2015-01-01

Objective: With further increase of CT numbers and their dominant contribution to medical exposure, there is a recent quest for more effective dose control. While reintroduction of iterative reconstruction (IR) has proved its potential in many applications, a novel focus is placed on more noise efficient detectors. Our purpose was to assess the potential of IR in combination with an integrated circuit detector (ICD) for aggressive dose reduction in head CT. Methods: Non-contrast low-dose head CT [190 mAs; weighted volume CT dose index (CTDIvol), 33.2 mGy] was performed in 50 consecutive patients, using a new noise efficient detector and IR. Images were assessed in terms of quantitative and qualitative image quality and compared with standard dose acquisitions (320 mAs; CTDIvol, 59.7 mGy) using a conventional detector and filtered back projection. Results: By combining ICD and IR in low-dose examinations, the signal to noise was improved by about 13% above the baseline level in the standard-dose control group. Both, contrast-to-noise ratio (2.02 ± 0.6 vs 1.88 ± 0.4; p = 0.18) and objective measurements of image sharpness (695 ± 84 vs 705 ± 151 change in Hounsfield units per pixel; p = 0.79) were fully preserved in the low-dose group. Likewise, there was no significant difference in the grading of several subjective image quality parameters when both noise-reducing strategies were used in low-dose examinations. Conclusion: Combination of noise efficient detector with IR allows for meaningful dose reduction in head CT without compromise of standard image quality. Advances in knowledge: Our study demonstrates the feasibility of almost 50% dose reduction in head CT dose (1.1 mSv per scan) through combination of novel dose-reducing strategies. PMID:25827204

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

PubMed

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

2016-03-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. Copyright © 2016 by the American Society of Nephrology.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

PubMed Central

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

2016-01-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology.

PubMed

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C; Morelli, John N

2017-01-01

We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms "interventional/computed tomography" and "radiation dose/radiation dose reduction." A PubMed query using the above-mentioned search terms for the years of 2005-2015 was performed. Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6-27) and 246±105 diagnostic radiology abstracts (range, 112-389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79-187) and 1205±307 publications (range, 829-1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology

PubMed Central

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C.; Morelli, John N.

2017-01-01

PURPOSE We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. METHODS Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms “interventional/computed tomography” and “radiation dose/radiation dose reduction.” A PubMed query using the above-mentioned search terms for the years of 2005–2015 was performed. RESULTS Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6–27) and 246±105 diagnostic radiology abstracts (range, 112–389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79–187) and 1205±307 publications (range, 829–1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). CONCLUSION The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted. PMID:28287072

Paediatric x-ray radiation dose reduction and image quality analysis.

PubMed

Martin, L; Ruddlesden, R; Makepeace, C; Robinson, L; Mistry, T; Starritt, H

2013-09-01

Collaboration of multiple staff groups has resulted in significant reduction in the risk of radiation-induced cancer from radiographic x-ray exposure during childhood. In this study at an acute NHS hospital trust, a preliminary audit identified initial exposure factors. These were compared with European and UK guidance, leading to the introduction of new factors that were in compliance with European guidance on x-ray tube potentials. Image quality was assessed using standard anatomical criteria scoring, and visual grading characteristics analysis assessed the impact on image quality of changes in exposure factors. This analysis determined the acceptability of gradual radiation dose reduction below the European and UK guidance levels. Chest and pelvis exposures were optimised, achieving dose reduction for each age group, with 7%-55% decrease in critical organ dose. Clinicians confirmed diagnostic image quality throughout the iterative process. Analysis of images acquired with preliminary and final exposure factors indicated an average visual grading analysis result of 0.5, demonstrating equivalent image quality. The optimisation process and final radiation doses are reported for Carestream computed radiography to aid other hospitals in minimising radiation risks to children.

Angular on-line tube current modulation in multidetector CT examinations of children and adults: The influence of different scanning parameters on dose reduction

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

Papadakis, Antonios E.; Perisinakis, Kostas; Damilakis, John

2007-07-15

The purpose of this study was to assess the potential of angular on-line tube current modulation on dose reduction in pediatric and adult patients undergoing multidetector computed tomography (MDCT) examinations. Five physical anthropomorphic phantoms that simulate the average individual as neonate, 1-year-old, 5-year-old, 10-year-old, and adult were employed in the current study. Phantoms were scanned with the use of on-line tube current modulation (TCM). Percent dose reduction (%DR) factors achieved by applying TCM, were determined for standard protocols used for head and neck, shoulder, thorax, thorax and abdomen, abdomen, abdomen and pelvis, pelvis, and whole body examinations. A preliminary studymore » on the application of TCM in MDCT examinations of adult patients was performed to validate the results obtained in anthropomorphic phantoms. Dose reduction was estimated as the percentage difference of the modulated milliamperes for each scan and the preset milliamperes prescribed by the scan protocol. The dose reduction in children was found to be much lower than the corresponding reduction achieved for adults. For helical scans the %DR factors, ranged between 1.6% and 7.4% for the neonate, 2.9% and 8.7% for the 1-year old, 2% and 6% for the 5-year-old, 5% and 10.9% for the 10-year-old, and 10.4% and 20.7% for the adult individual. For sequential scans the corresponding %DR factors ranged between 1.3% and 6.7%, 4.5% and 11%, 4.2% and 6.6%, 6.4% and 12.3%, and 8.9% and 23.3%, respectively. Broader beam collimations are associated with decreased %DR factors, when other scanning parameters are held constant. TCM did not impair image noise. In adult patients, the %DR values were found to be in good agreement with the corresponding results obtained in the anthropomorphic adult phantom. In conclusion, on-line TCM may be considered as a valuable tool for reducing dose in routine CT examinations of pediatric and adult patients. However, the dose reduction achieved with TCM in neonates and young children was found to be lower than that obtained for adults. Therefore, on-line TCM should work as an additional means to reduce dose and should not replace other conventional means of reducing dose, especially in neonates and young children.« less

Population PK-PD analyses of CD25 occupancy, CD56bright NK cell expansion, and regulatory T cell reduction by daclizumab HYP in subjects with multiple sclerosis.

PubMed

Diao, Lei; Hang, Yaming; Othman, Ahmed A; Mehta, Devangi; Amaravadi, Lakshmi; Nestorov, Ivan; Tran, Jonathan Q

2016-11-01

Daclizumab high yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α-subunit of the interleukin-2 receptor and is being developed for treatment of multiple sclerosis (MS). This manuscript characterized the pharmacokinetic-pharmacodynamic (PK-PD) relationships of daclizumab HYP in subjects with MS. Approximately 1400 subjects and 7000 PD measurements for each of three biomarkers [CD25 occupancy, CD56 bright natural killer (NK) cell count, regulatory T cell (Treg) count] from four clinical trials were analyzed using non-linear mixed effects modelling. Evaluated regimens included 150 or 300 mg subcutaneous (s.c.) every 4 weeks. CD25 occupancy was characterized using a sigmoidal maximum response (E max ) model. Upon daclizumab HYP treatment, CD25 saturation was rapid with complete saturation occurring after approximately 7 h and maintained when daclizumab HYP serum concentration was ≥5 mg l -1 . After the last 150 mg s.c. dose, unoccupied CD25 returned to baseline levels in approximately 24 weeks, with daclizumab HYP serum concentration approximately ≤1 mgl -1 1L. CD56 bright NK cell expansion was characterized using an indirect response model. Following daclizumab HYP 150 mg s.c. every 4 weeks, expansion plateaus approximately at week 36, at which the average maximum expansion ratio is 5.2. After the last dose, CD56 bright NK cells gradually declined to baseline levels within 24 weeks. Treg reduction was characterized by a sigmoidal E max model. Average maximum reduction of 60% occurred approximately 4 days post 150 mg s.c. dose. After the last dose, Tregs were projected to return to baseline levels in approximately 20 weeks. Robust PK-PD models of CD25 occupancy, CD56 bright NK cell expansion and Treg reduction by daclizumab HYP were developed to characterize its key pharmacodynamic effects in the target patient population. © 2016 The British Pharmacological Society.

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Sinogram noise reduction for low-dose CT by statistics-based nonlinear filters

NASA Astrophysics Data System (ADS)

Wang, Jing; Lu, Hongbing; Li, Tianfang; Liang, Zhengrong

2005-04-01

Low-dose CT (computed tomography) sinogram data have been shown to be signal-dependent with an analytical relationship between the sample mean and sample variance. Spatially-invariant low-pass linear filters, such as the Butterworth and Hanning filters, could not adequately handle the data noise and statistics-based nonlinear filters may be an alternative choice, in addition to other choices of minimizing cost functions on the noisy data. Anisotropic diffusion filter and nonlinear Gaussian filters chain (NLGC) are two well-known classes of nonlinear filters based on local statistics for the purpose of edge-preserving noise reduction. These two filters can utilize the noise properties of the low-dose CT sinogram for adaptive noise reduction, but can not incorporate signal correlative information for an optimal regularized solution. Our previously-developed Karhunen-Loeve (KL) domain PWLS (penalized weighted least square) minimization considers the signal correlation via the KL strategy and seeks the PWLS cost function minimization for an optimal regularized solution for each KL component, i.e., adaptive to the KL components. This work compared the nonlinear filters with the KL-PWLS framework for low-dose CT application. Furthermore, we investigated the nonlinear filters for post KL-PWLS noise treatment in the sinogram space, where the filters were applied after ramp operation on the KL-PWLS treated sinogram data prior to backprojection operation (for image reconstruction). By both computer simulation and experimental low-dose CT data, the nonlinear filters could not outperform the KL-PWLS framework. The gain of post KL-PWLS edge-preserving noise filtering in the sinogram space is not significant, even the noise has been modulated by the ramp operation.

Radiation dose reduction to the breast in thoracic CT: Comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current

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

Wang Jia; Duan Xinhui; Christner, Jodie A.

2011-11-15

Purpose: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. Methods: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ-based TCM; and (4)more » scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. Results: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ-based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. Conclusions: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for both pediatric and adult phantoms. However, organ-based TCM does not affect image noise or CT number accuracy, both of which are adversely affected by bismuth shielding. Alternatively, globally decreasing the tube current can produce the same dose reduction to the breast as bismuth shielding, with a similar noise increase, yet without the streak artifacts and CT number errors caused by the bismuth shields. Moreover, globally decreasing the tube current reduces the dose to all tissues scanned, not simply to the breast.« less

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

PubMed

Akdim, Fatima; Tribble, Diane L; Flaim, JoAnn D; Yu, Rosie; Su, John; Geary, Richard S; Baker, Brenda F; Fuhr, Rainard; Wedel, Mark K; Kastelein, John J P

2011-11-01

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia. Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued. Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Efficacy of a Radiation Absorbing Shield in Reducing Dose to the Interventionalist During Peripheral Endovascular Procedures: A Single Centre Pilot Study

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

Power, S.; Mirza, M.; Thakorlal, A.

PurposeThis prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures.Materials and MethodsA commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used tomore » measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated.ResultsTLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142).ConclusionInitial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator’s body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.« less

Dose-Response Analysis of Developmental Iodide Deficiency: Reductions in Thyroid Hormones and Impaired Hippocampal Synaptic Transmission

EPA Science Inventory

Iodide is an essential nutrient for thyroid hormone synthesis and severe iodide deficiency (ID) during early development is associated with neurological impairments. Several environmental contaminants can perturb the thyroid axis and this perturbation may be more acute under cond...

TU-AB-201-08: Rotating Shield High Dose Rate Brachytherapy with 153Gd and 75Se Isotopes

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

Renaud, M; Seuntjens, J; Enger, S

Purpose: To introduce rotating shield brachytherapy (RSBT) for different cancer sites with {sup 153}Gd and {sup 75}Se isotopes. RSBT is a form of intensity modulated brachytherapy, using shielded rotating catheters to provide a better dose distribution in the tumour while protecting healthy tissue. Methods: BrachySource, a Geant4-based Monte Carlo dose planning system was developed for investigation of RSBT with {sup 153}Gd and {sup 75}Se for different cancer sites. Dose distributions from {sup 153}Gd, {sup 75}Se and {sup 192}Ir isotopes were calculated in a 40 cm radius water phantom by using the microSelectron-v2 source model. The source was placed inside amore » cylindrical platinum shield with 1.3 mm diameter. An emission window coinciding with the active core of the source was created by removing half (180°) of the wall of the shield. Relative dose rate distributions of the three isotopes were simulated. As a proof of concept, a breast cancer patient originally treated with Mammosite was re-simulated with unshielded {sup 192}Ir and shielded {sup 153}Gd. Results: The source with the lowest energy, {sup 153}Gd, decreased the dose on the shielded side by 91%, followed by {sup 75}Se and {sup 192}Ir with 36% and 16% reduction at 1 cm from the source. The breast cancer patient simulation showed the ability of shielded {sup 153}Gd to spare the chest wall by a 90% dose reduction when only one emission window angle is considered. In this case, fully covering the PTV would require more delivery angles and the chest wall dose reduction would be less, however, the simulation demonstrates the potential of shielded {sup 153}Gd to selectively isolate organs at risk. Conclusion: Introducing {sup 153}Gd and {sup 75}Se sources combined with RSBT will allow escalation of dose in the target volume while maintaining low doses in radiation sensitive healthy tissue. Tailoring treatments to each individual patient by treating all parts of the tumour without over-irradiation of normal tissues will be possible. The author acknowledges partial support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290), and the Quebec Fonds de recherche Nature et Technologies.« less

Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

PubMed

Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

2013-01-01

After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

Quantitative Systems Pharmacology Model of NO Metabolome and Methemoglobin Following Long-Term Infusion of Sodium Nitrite in Humans

PubMed Central

Vega-Villa, K; Pluta, R; Lonser, R; Woo, S

2013-01-01

A long-term sodium nitrite infusion is intended for the treatment of vascular disorders. Phase I data demonstrated a significant nonlinear dose-exposure-toxicity relationship within the therapeutic dosage range. This study aims to develop a quantitative systems pharmacology model characterizing nitric oxide (NO) metabolome and methemoglobin after sodium nitrite infusion. Nitrite, nitrate, and methemoglobin concentration–time profiles in plasma and RBC were used for model development. Following intravenous sodium nitrite administration, nitrite undergoes conversion in RBC and tissue. Nitrite sequestered by RBC interacts more extensively with deoxyhemoglobin, which contributes greatly to methemoglobin formation. Methemoglobin is formed less-than-proportionally at higher nitrite doses as characterized with facilitated methemoglobin removal. Nitrate-to-nitrite reduction occurs in tissue and via entero-salivary recirculation. The less-than-proportional increase in nitrite and nitrate exposure at higher nitrite doses is modeled with a dose-dependent increase in clearance. The model provides direct insight into NO metabolome disposition and is valuable for nitrite dosing selection in clinical trials. PMID:23903463

Model-based iterative reconstruction for reduction of radiation dose in abdominopelvic CT: comparison to adaptive statistical iterative reconstruction.

PubMed

Yasaka, Koichiro; Katsura, Masaki; Akahane, Masaaki; Sato, Jiro; Matsuda, Izuru; Ohtomo, Kuni

2013-12-01

To evaluate dose reduction and image quality of abdominopelvic computed tomography (CT) reconstructed with model-based iterative reconstruction (MBIR) compared to adaptive statistical iterative reconstruction (ASIR). In this prospective study, 85 patients underwent referential-, low-, and ultralow-dose unenhanced abdominopelvic CT. Images were reconstructed with ASIR for low-dose (L-ASIR) and ultralow-dose CT (UL-ASIR), and with MBIR for ultralow-dose CT (UL-MBIR). Image noise was measured in the abdominal aorta and iliopsoas muscle. Subjective image analyses and a lesion detection study (adrenal nodules) were conducted by two blinded radiologists. A reference standard was established by a consensus panel of two different radiologists using referential-dose CT reconstructed with filtered back projection. Compared to low-dose CT, there was a 63% decrease in dose-length product with ultralow-dose CT. UL-MBIR had significantly lower image noise than L-ASIR and UL-ASIR (all p<0.01). UL-MBIR was significantly better for subjective image noise and streak artifacts than L-ASIR and UL-ASIR (all p<0.01). There were no significant differences between UL-MBIR and L-ASIR in diagnostic acceptability (p>0.65), or diagnostic performance for adrenal nodules (p>0.87). MBIR significantly improves image noise and streak artifacts compared to ASIR, and can achieve radiation dose reduction without severely compromising image quality.

Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats.

PubMed

Shin, Jae-Ho; Kim, Tae Sung; Kang, Il Hyun; Kang, Tae Seok; Moon, Hyun Ju; Han, Soon-Young

2009-10-01

To examine the effects of diethylstilbestrol (DES) on male pubertal development and thyroid function, juvenile male Sprague-Dawley rats were given DES daily by oral intubation at doses of 10, 20 and 40 microg/kg/day from postnatal day 33 for 20 days. Prepuce separation was significantly delayed at the dose of 20 microg/kg/day and above in the DES-treated rats. DES treatment induced a significant reduction in the weights of testes, epididymides, the ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani bulbocavernosus muscles, Cowper's glands and the glans penis. The weights of the liver and adrenals increased in the DES-treated animals. DES caused a dose-dependent reduction in germ cells; in particular the spermatids were mainly affected. The serum levels of testosterone and luteinizing hormone were significantly reduced in the DES-treated groups, but that of estradiol decreased. No differences were observed in the serum thyroxine levels of the control and DES-treated groups. In microscopic observation of the DES-treated animals, degeneration of germ cells and tubular atrophy in the testis were noted, but there were no microscopic changes in the thyroid. These results indicate that DES affected the pubertal development of juvenile male rats and that its mode of action may be related to alterations in hormone levels.

CT Fluoroscopy Shielding: Decreases in Scattered Radiation for the Patient and Operator

PubMed Central

Neeman, Ziv; Dromi, Sergio A.; Sarin, Shawn; Wood, Bradford J.

2008-01-01

PURPOSE High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator’s torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. PMID:17185699

Effects of dose reduction on bone strength prediction using finite element analysis

NASA Astrophysics Data System (ADS)

Anitha, D.; Subburaj, Karupppasamy; Mei, Kai; Kopp, Felix K.; Foehr, Peter; Noel, Peter B.; Kirschke, Jan S.; Baum, Thomas

2016-12-01

This study aimed to evaluate the effect of dose reduction, by means of tube exposure reduction, on bone strength prediction from finite-element (FE) analysis. Fresh thoracic mid-vertebrae specimens (n = 11) were imaged, using multi-detector computed tomography (MDCT), at different intensities of X-ray tube exposures (80, 150, 220 and 500 mAs). Bone mineral density (BMD) was estimated from the mid-slice of each specimen from MDCT images. Differences in image quality and geometry of each specimen were measured. FE analysis was performed on all specimens to predict fracture load. Paired t-tests were used to compare the results obtained, using the highest CT dose (500 mAs) as reference. Dose reduction had no significant impact on FE-predicted fracture loads, with significant correlations obtained with reference to 500 mAs, for 80 mAs (R2  = 0.997, p < 0.001), 150 mAs (R2 = 0.998, p < 0.001) and 220 mAs (R2 = 0.987, p < 0.001). There were no significant differences in volume quantification between the different doses examined. CT imaging radiation dose could be reduced substantially to 64% with no impact on strength estimates obtained from FE analysis. Reduced CT dose will enable early diagnosis and advanced monitoring of osteoporosis and associated fracture risk.

MO-PIS-Exhibit Hall-01: Imaging: CT Dose Optimization Technologies I

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

Denison, K; Smith, S

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The imaging topic this year is CT scanner dose optimization capabilities. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Dose Optimization Capabilities of GE Computed Tomography Scanners Presentation Time: 11:15 – 11:45 AM GE Healthcare is dedicated to the delivery of high quality clinical images through the development of technologies, whichmore » optimize the application of ionizing radiation. In computed tomography, dose management solutions fall into four categories: employs projection data and statistical modeling to decrease noise in the reconstructed image - creating an opportunity for mA reduction in the acquisition of diagnostic images. Veo represents true Model Based Iterative Reconstruction (MBiR). Using high-level algorithms in tandem with advanced computing power, Veo enables lower pixel noise standard deviation and improved spatial resolution within a single image. Advanced Adaptive Image Filters allow for maintenance of spatial resolution while reducing image noise. Examples of adaptive image space filters include Neuro 3-D filters and Cardiac Noise Reduction Filters. AutomA adjusts mA along the z-axis and is the CT equivalent of auto exposure control in conventional x-ray systems. Dynamic Z-axis Tracking offers an additional opportunity for dose reduction in helical acquisitions while SmartTrack Z-axis Tracking serves to ensure beam, collimator and detector alignment during tube rotation. SmartmA provides angular mA modulation. ECG Helical Modulation reduces mA during the systolic phase of the heart cycle. SmartBeam optimization uses bowtie beam-shaping hardware and software to filter off-axis x-rays - minimizing dose and reducing x-ray scatter. The DICOM Radiation Dose Structured Report (RDSR) generates a dose report at the conclusion of every examination. Dose Check preemptively notifies CT operators when scan parameters exceed user-defined dose thresholds. DoseWatch is an information technology application providing vendor-agnostic dose tracking and analysis for CT (and all other diagnostic x-ray modalities) SnapShot Pulse improves coronary CTA dose management. VolumeShuttle uses two acquisitions to increase coverage, decrease dose, and conserve on contrast administration. Color-Coding for Kids applies the Broselow-Luten Pediatric System to facilitate pediatric emergency care and reduce medical errors. FeatherLight achieves dose optimization through pediatric procedure-based protocols. Adventure Series scanners provide a child-friendly imaging environment promoting patient cooperation with resultant reduction in retakes and patient motion. Philips CT Dose Optimization Tools and Advanced Reconstruction Presentation Time: 11:45 ‘ 12:15 PM The first part of the talk will cover “Dose Reduction and Dose Optimization Technologies” present in Philips CT Scanners. The main Technologies to be presented include: DoseRight and tube current modulation (DoseRight, Z-DOM, 3D-DOM, DoseRight Cardiac) Special acquisition modes Beam filtration and beam shapers Eclipse collimator and ClearRay collimator NanoPanel detector DoseRight will cover automatic tube current selection that automatically adjusts the dose for the individual patient. The presentation will explore the modulation techniques currently employed in Philips CT scanners and will include the algorithmic concepts as well as illustrative examples. Modulation and current selection technologies to be covered include the Automatic Current Selection component of DoseRight, ZDOM longitudinal dose modulation, 3D-DOM (combination of longitudinal and rotational dose modulation), Cardiac Dose right (an ECG based dose modulation scheme), and the DoseRight Index (DRI) IQ index. The special acquisition modes covers acquisition techniques such as prospective gating that is designed to reduce exposure to the patient through the Cardiac Step and Shoot scan mode. This mode can substitute the much higher dose retrospective scan modes for certain types of cardiac imaging. The beam filtration and beam shaper portion will discuss the variety of filtration and beam shaping configurations available on Philips scanners. This topic includes the x-ray beam characteristics, tube filtration as well as dose compensator characteristics. The Eclipse collimator, ClearRay collimator and the NanoPanel detector portion will discuss additional technologies specific to wide coverage CT that address some of the unique challenges encountered and techniques employed to optimize image quality and optimize dose utilization. The Eclipse collimator reduces extraneous exposure by actively blocking the radiation tails at either end of helical scans that do not contribute to the image generation. The ClearRay collimator and the NanoPanel detector optimize the quality of the signal that reaches the detectors by addressing the increased scattered radiation present in wide coverage and the NanoPanel detector adds superior electronic noise characteristics valuable when imaging at a low dose level. The second part of the talk will present “Advanced Reconstruction Technologies” currently available on Philips CT Scanners. The talk will cover filtered back projection (FBP), iDose4 and Iterative Model Reconstruction (IMR). Each reconstruction method will include a discussion of the algorithm as well as similarities and differences between the algorithms. Examples illustrating the merits of each algorithm will be presented, and techniques and metrics to characterize the performance of each type of algorithm will be presented. The Filtered Back projection portion will discuss and provide a brief summary of relevant standard image reconstruction techniques in common use, and discuss the common tradeoffs when using the FBP algorithm. The iDose4 portion will present the algorithms used for iDose4 as well the different levels. The meaning of different levels of iDose4 available will be presented and quantified. Guidelines for selection iDose4 parameters based on the imaging need will be explained. The different image quality goals available with iDose4 and specifically how iDose4 enables noise reduction, spatial resolution improvement or both will be explained. The approaches to leveraging the benefits of iDose4 such as improved spatial resolution, decreased noise, and artifact prevention will be described and quantified; and measurements and metrics behind the improvements will be presented. The image quality benefits in specific imaging situations as well as how to best combine the technology with other dose reduction strategies to ensure the best image quality at a given dose level will be presented. Insight into the IMR algorithm as well as contrast to the iDose4 techniques and performance characteristics will be discussed. Metrics and techniques for characterizing this class of algorithm and IQ performance will be presented. The image quality benefits and the dose reduction capabilities of IMR will be explored. Illustrative examples of the noise reduction, spatial resolution improvement, and low contrast detectability improvements of the reconstruction method will be presented: clinical cases and phantom measurements demonstrating the benefits of IMR in the areas of low dose imaging, spatial resolution and low contrast resolution are discussed and the technical details behind the measurements will be presented compared to both iDose4 and traditional filtered back projection (FBP)« less

The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

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

Aitken, R.; Wilson, R.A.

1989-12-01

The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstratemore » that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.« less

Development of probabilistic internal dosimetry computer code

NASA Astrophysics Data System (ADS)

Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki

2017-02-01

Internal radiation dose assessment involves biokinetic models, the corresponding parameters, measured data, and many assumptions. Every component considered in the internal dose assessment has its own uncertainty, which is propagated in the intake activity and internal dose estimates. For research or scientific purposes, and for retrospective dose reconstruction for accident scenarios occurring in workplaces having a large quantity of unsealed radionuclides, such as nuclear power plants, nuclear fuel cycle facilities, and facilities in which nuclear medicine is practiced, a quantitative uncertainty assessment of the internal dose is often required. However, no calculation tools or computer codes that incorporate all the relevant processes and their corresponding uncertainties, i.e., from the measured data to the committed dose, are available. Thus, the objective of the present study is to develop an integrated probabilistic internal-dose-assessment computer code. First, the uncertainty components in internal dosimetry are identified, and quantitative uncertainty data are collected. Then, an uncertainty database is established for each component. In order to propagate these uncertainties in an internal dose assessment, a probabilistic internal-dose-assessment system that employs the Bayesian and Monte Carlo methods. Based on the developed system, we developed a probabilistic internal-dose-assessment code by using MATLAB so as to estimate the dose distributions from the measured data with uncertainty. Using the developed code, we calculated the internal dose distribution and statistical values ( e.g. the 2.5th, 5th, median, 95th, and 97.5th percentiles) for three sample scenarios. On the basis of the distributions, we performed a sensitivity analysis to determine the influence of each component on the resulting dose in order to identify the major component of the uncertainty in a bioassay. The results of this study can be applied to various situations. In cases of severe internal exposure, the causation probability of a deterministic health effect can be derived from the dose distribution, and a high statistical value ( e.g., the 95th percentile of the distribution) can be used to determine the appropriate intervention. The distribution-based sensitivity analysis can also be used to quantify the contribution of each factor to the dose uncertainty, which is essential information for reducing and optimizing the uncertainty in the internal dose assessment. Therefore, the present study can contribute to retrospective dose assessment for accidental internal exposure scenarios, as well as to internal dose monitoring optimization and uncertainty reduction.

Method to monitor HC-SCR catalyst NOx reduction performance for lean exhaust applications

DOEpatents

Viola, Michael B [Macomb Township, MI; Schmieg, Steven J [Troy, MI; Sloane, Thompson M [Oxford, MI; Hilden, David L [Shelby Township, MI; Mulawa, Patricia A [Clinton Township, MI; Lee, Jong H [Rochester Hills, MI; Cheng, Shi-Wai S [Troy, MI

2012-05-29

A method for initiating a regeneration mode in selective catalytic reduction device utilizing hydrocarbons as a reductant includes monitoring a temperature within the aftertreatment system, monitoring a fuel dosing rate to the selective catalytic reduction device, monitoring an initial conversion efficiency, selecting a determined equation to estimate changes in a conversion efficiency of the selective catalytic reduction device based upon the monitored temperature and the monitored fuel dosing rate, estimating changes in the conversion efficiency based upon the determined equation and the initial conversion efficiency, and initiating a regeneration mode for the selective catalytic reduction device based upon the estimated changes in conversion efficiency.

Dose reduction of up to 89% while maintaining image quality in cardiovascular CT achieved with prospective ECG gating

NASA Astrophysics Data System (ADS)

Londt, John H.; Shreter, Uri; Vass, Melissa; Hsieh, Jiang; Ge, Zhanyu; Adda, Olivier; Dowe, David A.; Sabllayrolles, Jean-Louis

2007-03-01

We present the results of dose and image quality performance evaluation of a novel, prospective ECG-gated Coronary CT Angiography acquisition mode (SnapShot Pulse, LightSpeed VCT-XT scanner, GE Healthcare, Waukesha, WI), and compare it to conventional retrospective ECG gated helical acquisition in clinical and phantom studies. Image quality phantoms were used to measure noise, slice sensitivity profile, in-plane resolution, low contrast detectability and dose, using the two acquisition modes. Clinical image quality and diagnostic confidence were evaluated in a study of 31 patients scanned with the two acquisition modes. Radiation dose reduction in clinical practice was evaluated by tracking 120 consecutive patients scanned with the prospectively gated scan mode. In the phantom measurements, the prospectively gated mode resulted in equivalent or better image quality measures at dose reductions of up to 89% compared to non-ECG modulated conventional helical scans. In the clinical study, image quality was rated excellent by expert radiologist reviewing the cases, with pathology being identical using the two acquisition modes. The average dose to patients in the clinical practice study was 5.6 mSv, representing 50% reduction compared to a similar patient population scanned with the conventional helical mode.

Efficacy and Safety of Multiple Doses of Exenatide Once-Monthly Suspension in Patients With Type 2 Diabetes: A Phase II Randomized Clinical Trial.

PubMed

Wysham, Carol H; MacConell, Leigh; Hardy, Elise

2016-10-01

This study investigated the efficacy and safety of multiple exenatide once-monthly suspension (QMS) doses of exenatide-containing microspheres in Miglyol referenced against the clinical dose of exenatide once-weekly (QW) microspheres in aqueous solution. In this phase II, randomized, controlled, single-blind study, 121 adults (∼30/arm) with type 2 diabetes and HbA1c 7.1-11.0% (54-97 mmol/mol) were randomized 1:1:1:1 to subcutaneous exenatide QW 2 mg (self-administered) or exenatide QMS 5, 8, or 11 mg (caregiver-administered) for 20 weeks. The primary end point was change in HbA1c. At baseline, mean age was 50 years, HbA1c was 8.5% (69 mmol/mol), fasting plasma glucose (FPG) was 184 mg/dL, and body weight was 98 kg. At week 20, mean ± SD HbA1c reductions were -1.54% ± 1.26% with exenatide QW and -1.29% ± 1.07%, -1.31% ± 1.66%, and -1.45% ± 0.93% with exenatide QMS 5, 8, and 11 mg, respectively (evaluable population: n = 110). There were no significant differences in HbA1c reductions among the exenatide QMS doses. FPG reductions were -34 ± 48 mg/dL with exenatide QW and -25 ± 43, -30 ± 52, and -49 ± 49 mg/dL with exenatide QMS 5, 8, and 11 mg, respectively. Weight decreased with all treatments. For exenatide QMS, nausea (16.7-23.3%) and headache (16.7-26.7%) were the most common adverse events. No major or minor hypoglycemia occurred. All doses of exenatide QMS resulted in efficacy and tolerability profiles consistent with exenatide QW. These results combined with pharmacokinetic and pharmacodynamic modeling could inform dose selection for further development. © 2016 by the American Diabetes Association.

SU-F-J-39: Dose Reduction Strategy Using Attenuation-Based Tube Current Modulation Method in CBCT for IGRT

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

Son, K; Lee, H; Kim, C

2016-06-15

Purpose: To reduce radiation dose to the patients, tube current modulation (TCM) method has been actively used in diagnostic CT systems. However, TCM method has not yet been applied to a kV-CBCT system on a LINAC machine. The purpose of this study is to investigate whether the use of TCM method is desirable in kV-CBCT system for IGRT. We have developed an attenuation-based tube current modulation (a-TCM) method using the prior knowledge of treatment CT image of a patient. Methods: Patients go through a diagnostic CT scan for RT planning; therefore, using this prior information of CT images, one canmore » estimate the total attenuation of an x-ray through the patient body in a CBCT setting for radiation therapy. We performed a numerical study incorporating major factors into account such as polychromatic x-ray, scatter, noise, and bow-tie filter to demonstrate that a-TCM method can produce equivalent quality of images at reduced imaging radiation doses. Using the CT projector program, 680 projection images of the pediatric XCAT phantom were obtained both in conventional scanning condition, i.e., without modulating the tube current, and in the proposed a-TCM scanning condition. FDK reconstruction algorithm was used for image reconstruction, and the organ dose due to imaging radiation has been calculated in both cases and compared using GATE/Geant4 simulation toolkit. Results: Reconstructed CT images in the a-TCM method showed similar SSIM values and noise properties to the reference images acquired by the conventional CBCT. In addition, reduction of organ doses ranged from 12% to 27%. Conclusion: We have successfully demonstrated the feasibility and dosimetric merit of the a-TCM method for kV-CBCT, and envision that it can be a useful option of CBCT scanning that provides patient dose reduction without degrading image quality.« less

Medical management with diazepam for electrical status epilepticus during slow wave sleep in children.

PubMed

Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman

2014-03-01

Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.

PubMed

Wasserstein, Melissa P; Jones, Simon A; Soran, Handrean; Diaz, George A; Lippa, Natalie; Thurberg, Beth L; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F; Puga, Ana Cristina

2015-01-01

Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. All patients successfully reached 3.0mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4h across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. Copyright © 2015. Published by Elsevier Inc.

A combination of spatial and recursive temporal filtering for noise reduction when using region of interest (ROI) fluoroscopy for patient dose reduction in image guided vascular interventions with significant anatomical motion

NASA Astrophysics Data System (ADS)

Setlur Nagesh, S. V.; Khobragade, P.; Ionita, C.; Bednarek, D. R.; Rudin, S.

2015-03-01

Because x-ray based image-guided vascular interventions are minimally invasive they are currently the most preferred method of treating disorders such as stroke, arterial stenosis, and aneurysms; however, the x-ray exposure to the patient during long image-guided interventional procedures could cause harmful effects such as cancer in the long run and even tissue damage in the short term. ROI fluoroscopy reduces patient dose by differentially attenuating the incident x-rays outside the region-of-interest. To reduce the noise in the dose-reduced regions previously recursive temporal filtering was successfully demonstrated for neurovascular interventions. However, in cardiac interventions, anatomical motion is significant and excessive recursive filtering could cause blur. In this work the effects of three noise-reduction schemes, including recursive temporal filtering, spatial mean filtering, and a combination of spatial and recursive temporal filtering, were investigated in a simulated ROI dose-reduced cardiac intervention. First a model to simulate the aortic arch and its movement was built. A coronary stent was used to simulate a bioprosthetic valve used in TAVR procedures and was deployed under dose-reduced ROI fluoroscopy during the simulated heart motion. The images were then retrospectively processed for noise reduction in the periphery, using recursive temporal filtering, spatial filtering and a combination of both. Quantitative metrics for all three noise reduction schemes are calculated and are presented as results. From these it can be concluded that with significant anatomical motion, a combination of spatial and recursive temporal filtering scheme is best suited for reducing the excess quantum noise in the periphery. This new noise-reduction technique in combination with ROI fluoroscopy has the potential for substantial patient-dose savings in cardiac interventions.

Detection and characterization of lesions on low-radiation-dose abdominal CT images postprocessed with noise reduction filters.

PubMed

Kalra, Mannudeep K; Maher, Michael M; Blake, Michael A; Lucey, Brian C; Karau, Kelly; Toth, Thomas L; Avinash, Gopal; Halpern, Elkan F; Saini, Sanjay

2004-09-01

To assess the effect of noise reduction filters on detection and characterization of lesions on low-radiation-dose abdominal computed tomographic (CT) images. Low-dose CT images of abdominal lesions in 19 consecutive patients (11 women, eight men; age range, 32-78 years) were obtained at reduced tube currents (120-144 mAs). These baseline low-dose CT images were postprocessed with six noise reduction filters; the resulting postprocessed images were then randomly assorted with baseline images. Three radiologists performed independent evaluation of randomized images for presence, number, margins, attenuation, conspicuity, calcification, and enhancement of lesions, as well as image noise. Side-by-side comparison of baseline images with postprocessed images was performed by using a five-point scale for assessing lesion conspicuity and margins, image noise, beam hardening, and diagnostic acceptability. Quantitative noise and contrast-to-noise ratio were obtained for all liver lesions. Statistical analysis was performed by using the Wilcoxon signed rank test, Student t test, and kappa test of agreement. Significant reduction of noise was observed in images postprocessed with filter F compared with the noise in baseline nonfiltered images (P =.004). Although the number of lesions seen on baseline images and that seen on postprocessed images were identical, lesions were less conspicuous on postprocessed images than on baseline images. A decrease in quantitative image noise and contrast-to-noise ratio for liver lesions was noted with all noise reduction filters. There was good interobserver agreement (kappa = 0.7). Although the use of currently available noise reduction filters improves image noise and ameliorates beam-hardening artifacts at low-dose CT, such filters are limited by a compromise in lesion conspicuity and appearance in comparison with lesion conspicuity and appearance on baseline low-dose CT images. Copyright RSNA, 2004

Tumor control probability reduction in gated radiotherapy of non-small cell lung cancers: a feasibility study.

PubMed

Siochi, R Alfredo; Kim, Yusung; Bhatia, Sudershan

2014-10-16

We studied the feasibility of evaluating tumor control probability (TCP) reductions for tumor motion beyond planned gated radiotherapy margins. Tumor motion was determined from cone-beam CT projections acquired for patient setup, intrafraction respiratory traces, and 4D CTs for five non-small cell lung cancer (NSCLC) patients treated with gated radiotherapy. Tumors were subdivided into 1 mm sections whose positions and doses were determined for each beam-on time point. (The dose calculation model was verified with motion phantom measurements.) The calculated dose distributions were used to generate the treatment TCPs for each patient. The plan TCPs were calculated from the treatment planning dose distributions. The treatment TCPs were compared to the plan TCPs for various models and parameters. Calculated doses matched phantom measurements within 0.3% for up to 3 cm of motion. TCP reductions for excess motion greater than 5mm ranged from 1.7% to 11.9%, depending on model parameters, and were as high as 48.6% for model parameters that simulated an individual patient. Repeating the worst case motion for all fractions increased TCP reductions by a factor of 2 to 3, while hypofractionation decreased these reductions by as much as a factor of 3. Treatment motion exceeding gating margins by more than 5 mm can lead to considerable TCP reductions. Appropriate margins for excess motion are recommended, unless applying daily tumor motion verification and adjusting thegating window.

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.

Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers.

PubMed

Skerjanec, Andrej; Wang, Jixian; Maren, Kelly; Rojkjaer, Lisa

2010-02-01

Deferasirox, a newly developed iron chelator, was coadministered orally with either a known inducer of drug metabolism or with cosubstrates for cytochrome P450 (CYP) to characterize the potential for drug-drug interactions. In the induction assessment, single-dose deferasirox pharmacokinetics were obtained in the presence and absence of a repeated-dose regimen of rifampin. In the CYP3A interaction evaluation, midazolam and its active hydroxylated metabolite were assessed after single doses of midazolam in the presence and absence of steady-state concentrations of deferasirox. To test for interaction at the level of CPY2C8, single-dose repaglinide pharmacokinetics/pharmacodynamics were determined with and without repeated-dose administration of deferasirox. After rifampin, a significant reduction (44%) in plasma exposure (AUC) to deferasirox was observed. Upon coadministration of midazolam, there was a modest reduction of up to 22% in midazolam exposure (AUC, C(max)), suggesting a modest induction of CYP3A4/5 by deferasirox. Def erasirox caused increases in repaglinide plasma C(max) and AUC of 1.5-fold to over 2-fold, respectively, with little change in blood glucose measures. Specific patient prescribing recommendations were established when coadministering deferasirox with midazolam, repaglinide, and rifampin. These recommendations may also apply to other substrates of CYP3A4/5 and CYP2C8 or potent inducers of glucuronidation.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

PubMed Central

Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

2016-01-01

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

Estimating radiation dose to organs of patients undergoing conventional and novel multidetector CT exams using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Angel, Erin

Advances in Computed Tomography (CT) technology have led to an increase in the modality's diagnostic capabilities and therefore its utilization, which has in turn led to an increase in radiation exposure to the patient population. As a result, CT imaging currently constitutes approximately half of the collective exposure to ionizing radiation from medical procedures. In order to understand the radiation risk, it is necessary to estimate the radiation doses absorbed by patients undergoing CT imaging. The most widely accepted risk models are based on radiosensitive organ dose as opposed to whole body dose. In this research, radiosensitive organ dose was estimated using Monte Carlo based simulations incorporating detailed multidetector CT (MDCT) scanner models, specific scan protocols, and using patient models based on accurate patient anatomy and representing a range of patient sizes. Organ dose estimates were estimated for clinical MDCT exam protocols which pose a specific concern for radiosensitive organs or regions. These dose estimates include estimation of fetal dose for pregnant patients undergoing abdomen pelvis CT exams or undergoing exams to diagnose pulmonary embolism and venous thromboembolism. Breast and lung dose were estimated for patients undergoing coronary CTA imaging, conventional fixed tube current chest CT, and conventional tube current modulated (TCM) chest CT exams. The correlation of organ dose with patient size was quantified for pregnant patients undergoing abdomen/pelvis exams and for all breast and lung dose estimates presented. Novel dose reduction techniques were developed that incorporate organ location and are specifically designed to reduce close to radiosensitive organs during CT acquisition. A generalizable model was created for simulating conventional and novel attenuation-based TCM algorithms which can be used in simulations estimating organ dose for any patient model. The generalizable model is a significant contribution of this work as it lays the foundation for the future of simulating TCM using Monte Carlo methods. As a result of this research organ dose can be estimated for individual patients undergoing specific conventional MDCT exams. This research also brings understanding to conventional and novel close reduction techniques in CT and their effect on organ dose.

PWR Facility Dose Modeling Using MCNP5 and the CADIS/ADVANTG Variance-Reduction Methodology

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

Blakeman, Edward D; Peplow, Douglas E.; Wagner, John C

2007-09-01

The feasibility of modeling a pressurized-water-reactor (PWR) facility and calculating dose rates at all locations within the containment and adjoining structures using MCNP5 with mesh tallies is presented. Calculations of dose rates resulting from neutron and photon sources from the reactor (operating and shut down for various periods) and the spent fuel pool, as well as for the photon source from the primary coolant loop, were all of interest. Identification of the PWR facility, development of the MCNP-based model and automation of the run process, calculation of the various sources, and development of methods for visually examining mesh tally filesmore » and extracting dose rates were all a significant part of the project. Advanced variance reduction, which was required because of the size of the model and the large amount of shielding, was performed via the CADIS/ADVANTG approach. This methodology uses an automatically generated three-dimensional discrete ordinates model to calculate adjoint fluxes from which MCNP weight windows and source bias parameters are generated. Investigative calculations were performed using a simple block model and a simplified full-scale model of the PWR containment, in which the adjoint source was placed in various regions. In general, it was shown that placement of the adjoint source on the periphery of the model provided adequate results for regions reasonably close to the source (e.g., within the containment structure for the reactor source). A modification to the CADIS/ADVANTG methodology was also studied in which a global adjoint source is weighted by the reciprocal of the dose response calculated by an earlier forward discrete ordinates calculation. This method showed improved results over those using the standard CADIS/ADVANTG approach, and its further investigation is recommended for future efforts.« less

Converging stereotactic radiotherapy using kilovoltage X-rays: experimental irradiation of normal rabbit lung and dose-volume analysis with Monte Carlo simulation.

PubMed

Kawase, Takatsugu; Kunieda, Etsuo; Deloar, Hossain M; Tsunoo, Takanori; Seki, Satoshi; Oku, Yohei; Saitoh, Hidetoshi; Saito, Kimiaki; Ogawa, Eileen N; Ishizaka, Akitoshi; Kameyama, Kaori; Kubo, Atsushi

2009-10-01

To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

Radiation dose reduction in computed tomography: techniques and future perspective

PubMed Central

Yu, Lifeng; Liu, Xin; Leng, Shuai; Kofler, James M; Ramirez-Giraldo, Juan C; Qu, Mingliang; Christner, Jodie; Fletcher, Joel G; McCollough, Cynthia H

2011-01-01

Despite universal consensus that computed tomography (CT) overwhelmingly benefits patients when used for appropriate indications, concerns have been raised regarding the potential risk of cancer induction from CT due to the exponentially increased use of CT in medicine. Keeping radiation dose as low as reasonably achievable, consistent with the diagnostic task, remains the most important strategy for decreasing this potential risk. This article summarizes the general technical strategies that are commonly used for radiation dose management in CT. Dose-management strategies for pediatric CT, cardiac CT, dual-energy CT, CT perfusion and interventional CT are specifically discussed, and future perspectives on CT dose reduction are presented. PMID:22308169

FW-CADIS Method for Global and Semi-Global Variance Reduction of Monte Carlo Radiation Transport Calculations

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

Wagner, John C; Peplow, Douglas E.; Mosher, Scott W

2014-01-01

This paper presents a new hybrid (Monte Carlo/deterministic) method for increasing the efficiency of Monte Carlo calculations of distributions, such as flux or dose rate distributions (e.g., mesh tallies), as well as responses at multiple localized detectors and spectra. This method, referred to as Forward-Weighted CADIS (FW-CADIS), is an extension of the Consistent Adjoint Driven Importance Sampling (CADIS) method, which has been used for more than a decade to very effectively improve the efficiency of Monte Carlo calculations of localized quantities, e.g., flux, dose, or reaction rate at a specific location. The basis of this method is the development ofmore » an importance function that represents the importance of particles to the objective of uniform Monte Carlo particle density in the desired tally regions. Implementation of this method utilizes the results from a forward deterministic calculation to develop a forward-weighted source for a deterministic adjoint calculation. The resulting adjoint function is then used to generate consistent space- and energy-dependent source biasing parameters and weight windows that are used in a forward Monte Carlo calculation to obtain more uniform statistical uncertainties in the desired tally regions. The FW-CADIS method has been implemented and demonstrated within the MAVRIC sequence of SCALE and the ADVANTG/MCNP framework. Application of the method to representative, real-world problems, including calculation of dose rate and energy dependent flux throughout the problem space, dose rates in specific areas, and energy spectra at multiple detectors, is presented and discussed. Results of the FW-CADIS method and other recently developed global variance reduction approaches are also compared, and the FW-CADIS method outperformed the other methods in all cases considered.« less

A semi-mechanistic model of CP-690,550-induced reduction in neutrophil counts in patients with rheumatoid arthritis.

PubMed

Gupta, Pankaj; Friberg, Lena E; Karlsson, Mats O; Krishnaswami, Sriram; French, Jonathan

2010-06-01

CP-690,550, a selective inhibitor of the Janus kinase family, is being developed as an oral disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). A semi-mechanistic model was developed to characterize the time course of drug-induced absolute neutrophil count (ANC) reduction in a phase 2a study. Data from 264 RA patients receiving 6-week treatment (placebo, 5, 15, 30 mg bid) followed by a 6-week off-treatment period were analyzed. The model included a progenitor cell pool, a maturation chain comprising transit compartments, a circulation pool, and a feedback mechanism. The model was adequately described by system parameters (BASE(h), ktr(h), gamma, and k(circ)), disease effect parameters (DIS), and drug effect parameters (k(off) and k(D)). The disease manifested as an increase in baseline ANC and reduced maturation time due to increased demand from the inflammation site. The drug restored the perturbed system parameters to their normal values via an indirect mechanism. ANC reduction due to a direct myelosuppressive drug effect was not supported. The final model successfully described the dose- and time-dependent changes in ANC and predicted the incidence of neutropenia at different doses reasonably well.

Low radiation dose in computed tomography: the role of iodine

PubMed Central

Aschoff, Andrik J; Catalano, Carlo; Krix, Martin; Albrecht, Thomas

2017-01-01

Recent approaches to reducing radiation exposure during CT examinations typically utilize automated dose modulation strategies on the basis of lower tube voltage combined with iterative reconstruction and other dose-saving techniques. Less clearly appreciated is the potentially substantial role that iodinated contrast media (CM) can play in low-radiation-dose CT examinations. Herein we discuss the role of iodinated CM in low-radiation-dose examinations and describe approaches for the optimization of CM administration protocols to further reduce radiation dose and/or CM dose while maintaining image quality for accurate diagnosis. Similar to the higher iodine attenuation obtained at low-tube-voltage settings, high-iodine-signal protocols may permit radiation dose reduction by permitting a lowering of mAs while maintaining the signal-to-noise ratio. This is particularly feasible in first pass examinations where high iodine signal can be achieved by injecting iodine more rapidly. The combination of low kV and IR can also be used to reduce the iodine dose. Here, in optimum contrast injection protocols, the volume of CM administered rather than the iodine concentration should be reduced, since with high-iodine-concentration CM further reductions of iodine dose are achievable for modern first pass examinations. Moreover, higher concentrations of CM more readily allow reductions of both flow rate and volume, thereby improving the tolerability of contrast administration. PMID:28471242

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

PubMed

Younger, Jarred; Noor, Noorulain; McCue, Rebecca; Mackey, Sean

2013-02-01

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain. When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication. Copyright © 2013 by the American College of Rheumatology.

Effects of added PGX®, a novel functional fibre, on the glycaemic index of starchy foods.

PubMed

Brand-Miller, Jennie C; Atkinson, Fiona S; Gahler, Roland J; Kacinik, Veronica; Lyon, Michael R; Wood, Simon

2012-07-01

The development of lower-glycaemic index (GI) foods requires simple, palatable and healthy strategies. The objective of the present study was to determine the most effective dose of a novel viscous fibre supplement (PGX®) to be added to starchy foods to reduce their GI. Healthy subjects (n 10) consumed glucose sugar (50 g in water × 3) and six starchy foods with a range of GI values (52-72) along with 0 (inert fibre), 2.5 or 5 g granular PGX® dissolved in 250 ml water. GI testing according to ISO Standard 26,642-2010 was used to determine the reduction in GI. PGX® significantly reduced the GI of all six foods (P < 0.001), with an average reduction of 19 % for the 2.5 g dose and 30 % for the 5 g dose, equivalent to a reducing the GI by 7 and 15 units, respectively. Consuming small quantities of the novel functional fibre PGX®, mixed with water at the start of a meal, is an effective strategy to reduce the GI of common foods.

Drug interactions: volatile anesthetics and opioids.

PubMed

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

[ACE inhibitors and the kidney].

PubMed

Hörl, W H

1996-01-01

Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

Effects of lasalocid or monensin on legume or grain (feedlot) bloat.

PubMed

Bartley, E E; Nagaraja, T G; Pressman, E S; Dayton, A D; Katz, M P; Fina, L R

1983-06-01

Doses of .66 to .99 mg monensin/kg body weight reduced legume bloat in cattle about 66% when compared with pretreatment bloat scores. Similar doses of lasalocid reduced legume bloat about 26%. A dose of 44 mg poloxalene/kg body weight (recommended dose for field use) reduced legume bloat 100%. Monensin or lasalocid combined with 25 or 50% of the recommended dose of poloxalene reduced bloat under that of the antibiotics alone, but did not achieve 100% reduction. The antibiotic thiopeptin provided no preventive effect on legume bloat. Lasalocid, monensin or an experimental polyether antibiotic (X-14,547 A) at a dose of 1.32 mg/kg body weight when tested on cattle bloated on high grain diets reduced bloat by 92, 64 and 25%, respectively. Lasalocid at .66 mg/kg effectively prevented bloat from developing when given to animals before the feeding of high grain diets; however, a 1.32-mg dose was required to control bloat in cattle that were already bloating before they were given lasalocid. A dose of 1.32 mg salinomycin was ineffective in controlling grain bloat.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Significant Radiation Dose Reduction in the Hybrid Operating Room Using a Novel X-ray Imaging Technology.

PubMed

van den Haak, R F F; Hamans, B C; Zuurmond, K; Verhoeven, B A N; Koning, O H J

2015-10-01

To prospectively quantify radiation dose change in aortoiliac endovascular procedures in the hybrid operating room (OR) for patients and medical staff with a novel X-ray imaging technology (ClarityIQ technology), and to assess whether procedure or fluoroscopy time or dose of iodinated contrast was affected. A prospective study including 138 patients was performed to compare radiation dose before and after installation of a novel X-ray imaging technology. Endovascular aneurysm repair (EVAR) was performed in 37 patients and an endovascular procedure for aortoiliac occlusive disease (AIOD) in 101. Patient radiation dose in air kerma (AK) and dose area product (DAP), patient demographics, and procedural data were recorded. Staff radiation dose was measured with real time personal dosimetry measurements. In both the EVAR and AIOD groups the reference system, ALX (AlluraXper FD20; Philips Healthcare, Best, the Netherlands), was compared with the upgraded X-ray system, CIQ (AlluraClarity FD20; Philips Healthcare). Procedure time, fluoroscopy time, and iodinated contrast dose were recorded. Patient radiation dose reduction in the EVAR group, in median AK, was 56% (ALX = 1,262.5 mGy; CIQ = 556.0 mGy [p < .01]); and in median DAP it was 57% (ALX = 224.4 Gycm(2) and CIQ = 95.8 Gycm(2) [p < .01]). Patient radiation dose reduction in the AIOD group, in median AK, was 76% (ALX = 1,011.0 mGy; CIQ = 248.0 mGy [p < .01]); and in median DAP it was 73% (ALX = 138.1 Gycm(2); CIQ = 38.0 Gycm(2) [p < .01]). Staff dose reduction in the EVAR group was 16% (ALX = 70.1 μSv; CIQ = 59.2 μSv [p = .43]) and in the AIOD group it was 69% (ALX = 96.2 μSv; CIQ = 30.1 μSv [p < .01]). There was no statistically significant difference between patient demographics, procedure time, fluoroscopy time, and iodinated contrast medium use in the two treatment groups before and after installation. A novel X-ray imaging technology in the hybrid OR suite resulted in a significant reduction of patient and staff radiation dose without affecting procedure length, fluoroscopy time, or use of contrast. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Reduction of radiation exposure while maintaining high-quality fluoroscopic images during interventional cardiology using novel x-ray tube technology with extra beam filtering.

PubMed

den Boer, A; de Feyter, P J; Hummel, W A; Keane, D; Roelandt, J R

1994-06-01

Radiographic technology plays an integral role in interventional cardiology. The number of interventions continues to increase, and the associated radiation exposure to patients and personnel is of major concern. This study was undertaken to determine whether a newly developed x-ray tube deploying grid-switched pulsed fluoroscopy and extra beam filtering can achieve a reduction in radiation exposure while maintaining fluoroscopic images of high quality. Three fluoroscopic techniques were compared: continuous fluoroscopy, pulsed fluoroscopy, and a newly developed high-output pulsed fluoroscopy with extra filtering. To ascertain differences in the quality of images and to determine differences in patient entrance and investigator radiation exposure, the radiated volume curve was measured to determine the required high voltage levels (kVpeak) for different object sizes for each fluoroscopic mode. The fluoroscopic data of 124 patient procedures were combined. The data were analyzed for radiographic projections, image intensifier field size, and x-ray tube kilovoltage levels (kVpeak). On the basis of this analysis, a reference procedure was constructed. The reference procedure was tested on a phantom or dummy patient by all three fluoroscopic modes. The phantom was so designed that the kilovoltage requirements for each projection were comparable to those needed for the average patient. Radiation exposure of the operator and patient was measured during each mode. The patient entrance dose was measured in air, and the operator dose was measured by 18 dosimeters on a dummy operator. Pulsed compared with continuous fluoroscopy could be performed with improved image quality at lower kilovoltages. The patient entrance dose was reduced by 21% and the operator dose by 54%. High-output pulsed fluoroscopy with extra beam filtering compared with continuous fluoroscopy improved the image quality, lowered the kilovoltage requirements, and reduced the patient entrance dose by 55% and the operator dose by 69%. High-output pulsed fluoroscopy with a grid-switched tube and extra filtering improves the image quality and significantly reduces both the operator dose and patient dose.

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review.

PubMed

Gebremedhn, Endale Gebreegziabher; Shortland, Peter John; Mahns, David Anthony

2018-04-12

Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle. A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy. Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m 2 ) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase. Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study.

PubMed

Greffier, Joël; Pereira, Fabricio; Macri, Francesco; Beregi, Jean-Paul; Larbi, Ahmed

2016-04-01

To evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR). Three anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom. The use of AEC produced a significant dose reduction (p<0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p<0.01) and reduced SNR and CNR (p<0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency. In chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Can use of adaptive statistical iterative reconstruction reduce radiation dose in unenhanced head CT? An analysis of qualitative and quantitative image quality

PubMed Central

Heggen, Kristin Livelten; Pedersen, Hans Kristian; Andersen, Hilde Kjernlie; Martinsen, Anne Catrine T

2016-01-01

Background Iterative reconstruction can reduce image noise and thereby facilitate dose reduction. Purpose To evaluate qualitative and quantitative image quality for full dose and dose reduced head computed tomography (CT) protocols reconstructed using filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Material and Methods Fourteen patients undergoing follow-up head CT were included. All patients underwent full dose (FD) exam and subsequent 15% dose reduced (DR) exam, reconstructed using FBP and 30% ASIR. Qualitative image quality was assessed using visual grading characteristics. Quantitative image quality was assessed using ROI measurements in cerebrospinal fluid (CSF), white matter, peripheral and central gray matter. Additionally, quantitative image quality was measured in Catphan and vendor’s water phantom. Results There was no significant difference in qualitative image quality between FD FBP and DR ASIR. Comparing same scan FBP versus ASIR, a noise reduction of 28.6% in CSF and between −3.7 and 3.5% in brain parenchyma was observed. Comparing FD FBP versus DR ASIR, a noise reduction of 25.7% in CSF, and −7.5 and 6.3% in brain parenchyma was observed. Image contrast increased in ASIR reconstructions. Contrast-to-noise ratio was improved in DR ASIR compared to FD FBP. In phantoms, noise reduction was in the range of 3 to 28% with image content. Conclusion There was no significant difference in qualitative image quality between full dose FBP and dose reduced ASIR. CNR improved in DR ASIR compared to FD FBP mostly due to increased contrast, not reduced noise. Therefore, we recommend using caution if reducing dose and applying ASIR to maintain image quality. PMID:27583169

Can use of adaptive statistical iterative reconstruction reduce radiation dose in unenhanced head CT? An analysis of qualitative and quantitative image quality.

PubMed

Østerås, Bjørn Helge; Heggen, Kristin Livelten; Pedersen, Hans Kristian; Andersen, Hilde Kjernlie; Martinsen, Anne Catrine T

2016-08-01

Iterative reconstruction can reduce image noise and thereby facilitate dose reduction. To evaluate qualitative and quantitative image quality for full dose and dose reduced head computed tomography (CT) protocols reconstructed using filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Fourteen patients undergoing follow-up head CT were included. All patients underwent full dose (FD) exam and subsequent 15% dose reduced (DR) exam, reconstructed using FBP and 30% ASIR. Qualitative image quality was assessed using visual grading characteristics. Quantitative image quality was assessed using ROI measurements in cerebrospinal fluid (CSF), white matter, peripheral and central gray matter. Additionally, quantitative image quality was measured in Catphan and vendor's water phantom. There was no significant difference in qualitative image quality between FD FBP and DR ASIR. Comparing same scan FBP versus ASIR, a noise reduction of 28.6% in CSF and between -3.7 and 3.5% in brain parenchyma was observed. Comparing FD FBP versus DR ASIR, a noise reduction of 25.7% in CSF, and -7.5 and 6.3% in brain parenchyma was observed. Image contrast increased in ASIR reconstructions. Contrast-to-noise ratio was improved in DR ASIR compared to FD FBP. In phantoms, noise reduction was in the range of 3 to 28% with image content. There was no significant difference in qualitative image quality between full dose FBP and dose reduced ASIR. CNR improved in DR ASIR compared to FD FBP mostly due to increased contrast, not reduced noise. Therefore, we recommend using caution if reducing dose and applying ASIR to maintain image quality.

Influence of different treatment techniques on radiation dose to the LAD coronary artery

PubMed Central

Nieder, Carsten; Schill, Sabine; Kneschaurek, Peter; Molls, Michael

2007-01-01

Background The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors. Methods Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). Results IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing. Conclusion IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage. PMID:17547777

Generative Adversarial Networks for Noise Reduction in Low-Dose CT.

PubMed

Wolterink, Jelmer M; Leiner, Tim; Viergever, Max A; Isgum, Ivana

2017-12-01

Noise is inherent to low-dose CT acquisition. We propose to train a convolutional neural network (CNN) jointly with an adversarial CNN to estimate routine-dose CT images from low-dose CT images and hence reduce noise. A generator CNN was trained to transform low-dose CT images into routine-dose CT images using voxelwise loss minimization. An adversarial discriminator CNN was simultaneously trained to distinguish the output of the generator from routine-dose CT images. The performance of this discriminator was used as an adversarial loss for the generator. Experiments were performed using CT images of an anthropomorphic phantom containing calcium inserts, as well as patient non-contrast-enhanced cardiac CT images. The phantom and patients were scanned at 20% and 100% routine clinical dose. Three training strategies were compared: the first used only voxelwise loss, the second combined voxelwise loss and adversarial loss, and the third used only adversarial loss. The results showed that training with only voxelwise loss resulted in the highest peak signal-to-noise ratio with respect to reference routine-dose images. However, CNNs trained with adversarial loss captured image statistics of routine-dose images better. Noise reduction improved quantification of low-density calcified inserts in phantom CT images and allowed coronary calcium scoring in low-dose patient CT images with high noise levels. Testing took less than 10 s per CT volume. CNN-based low-dose CT noise reduction in the image domain is feasible. Training with an adversarial network improves the CNNs ability to generate images with an appearance similar to that of reference routine-dose CT images.

Breast surface radiation dose during coronary CT angiography: reduction by breast displacement and lead shielding.

PubMed

Foley, Shane J; McEntee, Mark F; Achenbach, Stephan; Brennan, Patrick C; Rainford, Louise S; Dodd, Jonathan D

2011-08-01

The purpose of this study was to prospectively evaluate the effect of cranial breast displacement and lead shielding on in vivo breast surface radiation dose in women undergoing coronary CT angiography. Fifty-four women (mean age, 59.2 ± 9.8 years) prospectively underwent coronary 64-MDCT angiography for evaluation of chest pain. The patients were randomly assigned to a control group (n = 16), breast displacement group (n = 22), or breast displacement plus lead shielding group (n = 16). Thermoluminescent dosimeters (TLDs) were placed superficially on each breast quadrant and the areolar region of both breasts. Breast surface radiation doses, the degree of breast displacement, and coronary image quality were compared between groups. A phantom dose study was conducted to compare breast doses with z-axis positioning on the chest wall. A total of 1620 TLD dose measurements were recorded. Compared with control values, the mean breast surface dose was reduced 23% in the breast displacement group (24.3 vs 18.6 mGy, p = 0.015) and 36% in the displacement plus lead shielding group (24.3 vs 15.6 mGy, p = 0.0001). Surface dose reductions were greatest in the upper outer (displacement alone, 66%; displacement plus shielding, 63%), upper inner (65%, 58%), and areolar quadrants (44%, 53%). The smallest surface dose reductions were recorded for A-cup breasts: 7% for the displacement group and 3% for the displacement plus lead group (p = 0.741). Larger reductions in surface dose were recorded for B-cup (25% and 56%, p = 0.273), C-cup (38% and 60%, p = 0.001), and D-cup (31% and 25%, p = 0.095) sizes. Most of the patients (79%) had either good (< 50% of breast above scan range) or excellent (< 75% of breast above the scan range) breast displacement. No significant difference in coronary image quality was detected between groups. The phantom dose study showed that surface TLD measurements were underestimates of absorbed tissue dose by a mean of 9% and that a strong negative correlation exists between the amount of cranial displacement and breast dose. Use of breast displacement during coronary CTA substantially reduces the radiation dose to the breast surface.

Dose comparison between conventional and quasi-monochromatic systems for diagnostic radiology

NASA Astrophysics Data System (ADS)

Baldelli, P.; Taibi, A.; Tuffanelli, A.; Gambaccini, M.

2004-09-01

Several techniques have been introduced in the last year to reduce the dose to the patient by minimizing the risk of tumour induced by radiation. In this work the radiological potential of dose reduction in quasi-monochromatic spectra produced via mosaic crystal Bragg diffraction has been evaluated, and a comparison with conventional spectra has been performed for four standard examinations: head, chest, abdomen and lumbar sacral spine. We have simulated quasi-monochromatic x-rays with the Shadow code, and conventional spectra with the Spectrum Processor. By means of the PCXMC software, we have simulated four examinations according to parameters established by the European Guidelines, and calculated absorbed dose for principal organs and the effective dose. Simulations of quasi-monochromatic laminar beams have been performed without anti-scatter grid, because of their inherent scatter geometry, and compared with simulations with conventional beams with anti-scatter grids. Results have shown that the dose reduction due to the introduction of quasi-monochromatic x-rays depends on different parameters related to the quality of the beam, the organ composition and the anti-scatter grid. With parameters chosen in this study a significant dose reduction can be achieved for two out of four kinds of examination.

Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey.

PubMed

Thomas, P; Hayton, A; Beveridge, T; Marks, P; Wallace, A

2015-09-01

To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. This study examines the impact of the use of IR on patient dose in CT on a national scale.

The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure.

PubMed

Perez, Alfonso; Cao, Charlie

2017-03-01

In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d. ©2016 Wiley Periodicals, Inc.

DECREASE Final Technical Report: Development of a Commercial Ready Enzyme Application System for Ethanol

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

Teter, Sarah A

Conversion of biomass to sugars plays a central in reducing our dependence on petroleum, as it allows production of a wide range of biobased fuels and chemicals, through fermentation of those sugars. The DECREASE project delivers an effective enzyme cocktail for this conversion, enabling reduced costs for producing advanced biofuels such as cellulosic ethanol. Benefits to the public contributed by growth of the advanced biofuels industry include job creation, economic growth, and energy security. The DECREASE primary project objective was to develop a two-fold improved enzyme cocktail, relative to an advanced cocktail (CZP00005) that had been developed previously (from 2000-more » 2007). While the final milestone was delivery of all enzyme components as an experimental mixture, a secondary objective was to deploy an improved cocktail within 3 years following the close of the project. In February 2012, Novozymes launched Cellic CTec3, a multi-enzyme cocktail derived in part from components developed under DECREASE. The externally validated performance of CTec3 and an additional component under project benchmarking conditions indicated a 1.8-fold dose reduction in enzyme dose required for 90% conversion (based on all available glucose and xylose sources) of NREL dilute acid pretreated PCS, relative to the starting advanced enzyme cocktail. While the ability to achieve 90% conversion is impressive, targeting such high levels of biomass digestion is likely not the most cost effective strategy. Novozymes techno economic modeling showed that for NREL's dilute acid pretreated corn stover (PCS), 80% target conversion enables a lower total production cost for cellulosic ethanol than for 90% conversion, and this was also found to be the case when cost assumptions were based on the NREL 2002 Design Report. A 1.8X dose-reduction was observed for 80% conversion in the small scale (50 g) DECREASE benchmark assay for CTec3 and an additional component. An upscaled experiment (in 0.5 kg kettle reactors) was performed to compare the starting enzyme mixture CZP00005 with CTec3 alone; these results indicated a 1.9X dose- reduction for 80% conversion. The CTec3 composition does not include the best available enzyme components from the DECREASE effort. While these components are not yet available in a commercial product, experimental mixtures were assayed in a smaller scale assay using DECREASE PCS, at high solids loadings (21.5% TS). The results indicated that the newer mixtures required 2.9X-less enzyme for 90% conversion, and 3.2X-less enzyme for 80% conversion, relative to the starting enzyme cocktail. In conclusion, CTec3 delivers a 1.8-1.9X dose reduction on NREL PCS at high solids loadings, and the next generation enzyme from Novozymes will continue to show dramatically improved biochemical performance. CTec3 allows reduced costs today, and the experimental cocktails point to continued biotechnological improvements that will further drive down costs for biorefineries of tomorrow.« less

Multi-Case Knowledge-Based IMRT Treatment Planning in Head and Neck Cancer

NASA Astrophysics Data System (ADS)

Grzetic, Shelby Mariah

Head and neck cancer (HNC) IMRT treatment planning is a challenging process that relies heavily on the planner's experience. Previously, we used the single, best match from a library of manually planned cases to semi-automatically generate IMRT plans for a new patient. The current multi-case Knowledge Based Radiation Therapy (MC-KBRT) study utilized different matching cases for each of six individual organs-at-risk (OARs), then combined those six cases to create the new treatment plan. From a database of 103 patient plans created by experienced planners, MC-KBRT plans were created for 40 (17 unilateral and 23 bilateral) HNC "query" patients. For each case, 2D beam's-eye-view images were used to find similar geometric "match" patients separately for each of 6 OARs. Dose distributions for each OAR from the 6 matching cases were combined and then warped to suit the query case's geometry. The dose-volume constraints were used to create the new query treatment plan without the need for human decision-making throughout the IMRT optimization. The optimized MC-KBRT plans were compared against the clinically approved plans and Version 1 (previous KBRT using only one matching case with dose warping) using the dose metrics: mean, median, and maximum (brainstem and cord+5mm) doses. Compared to Version 1, MC-KBRT had no significant reduction of the dose to any of the OARs in either unilateral or bilateral cases. Compared to the manually planned unilateral cases, there was significant reduction of the oral cavity mean/median dose (>2Gy) at the expense of the contralateral parotid. Compared to the manually planned bilateral cases, reduction of dose was significant in the ipsilateral parotid, larynx, and oral cavity (>3Gy mean/median) while maintaining PTV coverage. MC-KBRT planning in head and neck cancer generates IMRT plans with better dose sparing than manually created plans. MC-KBRT using multiple case matches does not show significant dose reduction compared to using a single match case with dose warping.

SU-C-12A-07: Effect of Vertical Position On Dose Reduction Using X-Care

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

Silosky, M; Marsh, R

Purpose: Reduction of absorbed dose to radiosensitive tissues is an important goal in diagnostic radiology. Siemens Medical has introduced a technique (X-CARE) to lower CT dose to anterior anatomy by reducing the tube current during 80° of rotation over radiosensitive tissues. Phantom studies have shown 30-40% dose reduction when phantoms are positioned at isocenter. However, for CT face and sinus exams, the center of the head is commonly positioned below isocenter. This work investigated the effects of vertical patient positioning on dose reduction using X-CARE. Methods: A 16cm Computed Tomography Dose Index phantom was scanned on a Siemens Definition Flashmore » CT scanner using a routine head protocol, with the phantom positioned at scanner isocenter. Optically stimulated luminescent dosimeters were placed on the anterior and posterior sides of the phantom. The phantom was lowered in increments of 2cm and rescanned, up to 8cm below isocenter. The experiment was then repeated using the same scan parameters but adding the X-CARE technique. The mean dosimeter counts were determined for each phantom position, and the difference between XCARE and routine scans was plotted as a function of distance from isocenter. Results: With the phantom positioned at isocenter, using XCARE reduced dose to the anterior side of the phantom by 40%, compared to dose when X-CARE was not used. Positioned below isocenter, anterior dose was reduced by only 20-27%. Additionally, using X-CARE at isocenter reduced dose to the anterior portion of the phantom by 45.6% compared to scans performed without X-CARE 8cm below isocenter. Conclusion: While using X-CARE substantially reduced dose to the anterior side of the phantom, this effect was diminished when the phantom was positioned below isocenter, simulating common practice for face and sinus scans. This indicates that centering the head in the gantry will maximize the effect of X-CARE.« less

Proton therapy to the subdiaphragmatic region in the management of patients with Hodgkin lymphoma.

PubMed

Sachsman, Suzanne; Hoppe, Bradford S; Mendenhall, Nancy P; Holtzman, Adam; Li, Zuofeng; Slayton, William; Joyce, Mike; Sandler, Eric; Flampouri, Stella

2015-07-01

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

Effect of external shielding for neutrons during radiotherapy for prostate cancer, considering the 2300 CD linear accelerator and voxel phantom

NASA Astrophysics Data System (ADS)

Thalhofer, J. L.; Roque, H. S.; Rebello, W. F.; Correa, S. A.; Silva, A. X.; Souza, E. M.; Batita, D. V. S.; Sandrini, E. S.

2014-02-01

Photoneutron production occurs when high energy photons, greater than 6.7 MeV, interact with linear accelerator head structures. In Brazil, the National Cancer Institute, one of the centers of reference in cancer treatment, uses radiation at 4 angles (0°, 90°, 180° and 270°) as treatment protocol for prostate cancer. With the objective of minimizing the dose deposited in the patient due to photoneutrons, this study simulated radiotherapy treatment using MCNPX, considering the most realistic environment; simulating the radiotherapy room, the Linac 2300 head, the MAX phantom and the treatment protocol with the accelerator operating at 18 MV. In an attempt to reduce the dose deposited by photoneutrons, an external shielding was added to the Linac 2300. Results show that the equivalent dose due to photoneutrons deposited in the patient diminished. The biggest reduction was seen in bone structures, such as the tibia and fibula, and mandible, at approximately 75%. Besides that, organs such as the brain, pancreas, small intestine, lungs and thyroid revealed a reduction of approximately 60%. It can be concluded that the shielding developed by our research group is efficient in neutron shielding, reducing the dose for the patient, and thus, the risk of secondary cancer, and increasing patient survival rates.

A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma

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

Devereux, Thomas, E-mail: thomas.devereux@petermac.org; Pham, Daniel; Kron, Tomas

2015-04-01

This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dosemore » to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30 cm{sup 3} of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30 cm{sup 3} of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.« less

Behavioral and Psychological Predictors of Chemotherapy Adherence in Patients with Advanced Non-Small-Cell Lung Cancer

PubMed Central

Greer, Joseph A.; Pirl, William F.; Park, Elyse R.; Lynch, Thomas J.; Temel, Jennifer S.

2013-01-01

Objective Dose delays and reductions in chemotherapy due to hematologic toxicities are common among patients with advanced non-small-cell lung cancer (NSCLC). However, limited data exist on behavioral or psychological predictors of chemotherapy adherence. The goal of this study was to explore the frequency and clinical predictors of infusion dose delays and reductions in this patient population. Methods Fifty patients newly diagnosed with advanced NSCLC of high performance status (ECOG PS=0-1) completed baseline assessments on quality of life (FACT-L) and mood (HADS) within eight weeks of diagnosis. Participants were followed prospectively for six months. Chemotherapy dosing data came from medical chart review. Results All patients received chemotherapy during the course of the study, beginning with either a platinum-based doublet (74%), an oral epidermal growth factor receptor-tyrosine kinase inhibitor (14%), or a parenteral single agent (12%). Forty percent (N=20) of patients had either a dose delay (38%) and/or reduction (16%) in their scheduled infusions. Fisher’s exact tests showed that patients who experienced neutropenia, smoked at the time of diagnosis, or reported heightened baseline anxiety were significantly more likely to experience dose delays or reductions. There were no associations between chemotherapy adherence and patient demographics, performance status, or quality of life. Conclusion In this sample, over one-third of patients with advanced NSCLC experienced either a dose delay or reduction in prescribed chemotherapy regimens. Behavioral and psychological factors, such as tobacco use and anxiety symptoms, appear to play an important role in chemotherapy adherence, though further study is required to confirm these findings. PMID:19027443

Approaches to reducing photon dose calculation errors near metal implants

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

Huang, Jessie Y.; Followill, David S.; Howell, Reb

Purpose: Dose calculation errors near metal implants are caused by limitations of the dose calculation algorithm in modeling tissue/metal interface effects as well as density assignment errors caused by imaging artifacts. The purpose of this study was to investigate two strategies for reducing dose calculation errors near metal implants: implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) dose calculation method and use of metal artifact reduction methods for computed tomography (CT) imaging. Methods: Both error reduction strategies were investigated using a simple geometric slab phantom with a rectangular metal insert (composed of titanium or Cerrobend), as well asmore » two anthropomorphic phantoms (one with spinal hardware and one with dental fillings), designed to mimic relevant clinical scenarios. To assess the dosimetric impact of metal kernels, the authors implemented titanium and silver kernels in a commercial collapsed cone C/S algorithm. To assess the impact of CT metal artifact reduction methods, the authors performed dose calculations using baseline imaging techniques (uncorrected 120 kVp imaging) and three commercial metal artifact reduction methods: Philips Healthcare’s O-MAR, GE Healthcare’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI with metal artifact reduction software (MARS) applied. For the simple geometric phantom, radiochromic film was used to measure dose upstream and downstream of metal inserts. For the anthropomorphic phantoms, ion chambers and radiochromic film were used to quantify the benefit of the error reduction strategies. Results: Metal kernels did not universally improve accuracy but rather resulted in better accuracy upstream of metal implants and decreased accuracy directly downstream. For the clinical cases (spinal hardware and dental fillings), metal kernels had very little impact on the dose calculation accuracy (<1.0%). Of the commercial CT artifact reduction methods investigated, the authors found that O-MAR was the most consistent method, resulting in either improved dose calculation accuracy (dental case) or little impact on calculation accuracy (spine case). GSI was unsuccessful at reducing the severe artifacts caused by dental fillings and had very little impact on calculation accuracy. GSI with MARS on the other hand gave mixed results, sometimes introducing metal distortion and increasing calculation errors (titanium rectangular implant and titanium spinal hardware) but other times very successfully reducing artifacts (Cerrobend rectangular implant and dental fillings). Conclusions: Though successful at improving dose calculation accuracy upstream of metal implants, metal kernels were not found to substantially improve accuracy for clinical cases. Of the commercial artifact reduction methods investigated, O-MAR was found to be the most consistent candidate for all-purpose CT simulation imaging. The MARS algorithm for GSI should be used with caution for titanium implants, larger implants, and implants located near heterogeneities as it can distort the size and shape of implants and increase calculation errors.« less

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

PubMed

Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M

2013-09-01

Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

PubMed

El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

2013-10-01

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Measurements of air dose rates in and around houses in the Fukushima Prefecture in Japan after the Fukushima accident.

PubMed

Matsuda, Norihiro; Mikami, Satoshi; Sato, Tetsuro; Saito, Kimiaki

2017-01-01

Measurements of air dose rates for 192 houses in a less contaminated area (<0.5 μSv h -1 ) of the Fukushima Prefecture in Japan were conducted in both living rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters and around the houses via a man-borne survey at intervals of several meters. The relation of the two air dose rates (inside and outside) for each house, including the background from natural radionuclides, was divided into several categories, determined by construction materials (light and heavy) and floor number, with the dose reduction factors being expressed as the ratio of the dose inside to that outside the house. For wooden and lightweight steel houses (classed as light), the dose rates inside and outside the houses showed a positive correlation and linear regression with a slope-intercept form due to the natural background, although the degree of correlation was not very high. The regression coefficient, i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on the second floor. It was found that the contribution of natural radiation cannot be neglected when we consider dose reduction factors in less contaminated areas. The reductions in indoor dose rates are observed because a patch of ground under each house is not contaminated (this is the so-called uncontaminated effect) since the shielding capability of light construction materials is typically low. For reinforced steel-framed concrete houses (classed as heavy), the dose rates inside the houses did not show a correlation with those outside the houses due to the substantial shielding capability of these materials. The average indoor dose rates were slightly higher than the arithmetic mean value of the outdoor dose rates from the natural background because concrete acts as a source of natural radionuclides. The characteristics of the uncontaminated effect were clarified through Monte Carlo simulations. It was found that there is a great variation in air dose rates even within one house, depending on the height of the area and its closeness to the outside boundary. Measurements of outdoor dose rates required consideration of local variations depending on the environment surrounding each house. The representative value was obtained from detailed distributions of air dose rates around the house, as measured by a man-borne survey. Therefore, it is imperative to recognize that dose reduction factors fluctuate in response to various factors such as the size and shape of a house, construction materials acting as a shield and as sources, position (including height) within a room, floor number, total number of floors, and surrounding environment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Radiation dose reduction in CT with adaptive statistical iterative reconstruction (ASIR) for patients with bronchial carcinoma and intrapulmonary metastases.

PubMed

Schäfer, M-L; Lüdemann, L; Böning, G; Kahn, J; Fuchs, S; Hamm, B; Streitparth, F

2016-05-01

To compare the radiation dose and image quality of 64-row chest computed tomography (CT) in patients with bronchial carcinoma or intrapulmonary metastases using full-dose CT reconstructed with filtered back projection (FBP) at baseline and reduced dose with 40% adaptive statistical iterative reconstruction (ASIR) at follow-up. The chest CT images of patients who underwent FBP and ASIR studies were reviewed. Dose-length products (DLP), effective dose, and size-specific dose estimates (SSDEs) were obtained. Image quality was analysed quantitatively by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurement. In addition, image quality was assessed by two blinded radiologists evaluating images for noise, contrast, artefacts, visibility of small structures, and diagnostic acceptability using a five-point scale. The ASIR studies showed 36% reduction in effective dose compared with the FBP studies. The qualitative and quantitative image quality was good to excellent in both protocols, without significant differences. There were also no significant differences for SNR except for the SNR of lung surrounding the tumour (FBP: 35±17, ASIR: 39±22). A protocol with 40% ASIR can provide approximately 36% dose reduction in chest CT of patients with bronchial carcinoma or intrapulmonary metastases while maintaining excellent image quality. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Ultralow-dose computed tomography imaging for surgery of midfacial and orbital fractures using ASIR and MBIR.

PubMed

Widmann, G; Dalla Torre, D; Hoermann, R; Schullian, P; Gassner, E M; Bale, R; Puelacher, W

2015-04-01

The influence of dose reductions on diagnostic quality using a series of high-resolution ultralow-dose computed tomography (CT) scans for computer-assisted planning and surgery including the most recent iterative reconstruction algorithms was evaluated and compared with the fracture detectability of a standard cranial emergency protocol. A human cadaver head including the mandible was artificially prepared with midfacial and orbital fractures and scanned using a 64-multislice CT scanner. The CT dose index volume (CTDIvol) and effective doses were calculated using application software. Noise was evaluated as the standard deviation in Hounsfield units within an identical region of interest in the posterior fossa. Diagnostic quality was assessed by consensus reading of a craniomaxillofacial surgeon and radiologist. Compared with the emergency protocol at CTDIvol 35.3 mGy and effective dose 3.6 mSv, low-dose protocols down to CTDIvol 1.0 mGy and 0.1 mSv (97% dose reduction) may be sufficient for the diagnosis of dislocated craniofacial fractures. Non-dislocated fractures may be detected at CTDIvol 2.6 mGy and 0.3 mSv (93% dose reduction). Adaptive statistical iterative reconstruction (ASIR) 50 and 100 reduced average noise by 30% and 56%, and model-based iterative reconstruction (MBIR) by 93%. However, the detection rate of fractures could not be improved due to smoothing effects. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2005-05-01

of a cycle for over 7 days, the carboplatin dose will be decreased by 25% for subsequent cycles. For a second episode of febrile neutropenia , G-CSF...should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol treatment should be discontinued... neutropenia despite a dose reduction in the previous course. G-CSF may also be used as clinically indicated for neutropenic infection. 4.2.4 The use of

Pediatric CT and radiation: our responsibility

NASA Astrophysics Data System (ADS)

Frush, Donald P.

2009-02-01

In order to discuss the cost-benefit ratio of CT examinations in children, one must be familiar with the reasons why CT can provide a high collective or individual dose. The reasons include increasing CT use as well as lack of attention to dose reduction strategies. While those have been substantial efforts for dose reduction, additional work is necessary to prevent unnecessary radiation exposure. This responsibility is shared between science and medicine, industry, regulatory agencies, and patients as well.

Effectiveness of disinfectant treatments for inactivating Piscirickettsia salmonis.

PubMed

Muniesa, A; Escobar-Dodero, J; Silva, N; Henríquez, P; Bustos, P; Perez, A M; Mardones, F O

2018-03-08

This short communication investigated in vitro differences between commercial disinfectants types (n = 36), doses of application, and time of action in the elimination of Piscirickettsia salmonis, the most important bacterium affecting farmed salmon in Chile. Seven different treatments were examined, including active and inactive chlorine dioxides, glutaraldehyde, hypochlorite disinfectants and detergents, peracetic acid, peroxides and other miscellaneous methods A 3 replicate set of each of the sample groups was stored at 20 °C and 95% relative humidity and retested after 1, 5 and 30 min with varying doses (low, recommended and high doses). Multiple comparison tests were performed for the mean log CFU/ml among different disinfectant types, dose (ppm) and time of exposure (minutes) on the reduction of P. salmonis. Overall, disinfection using peracetic acid, peroxides, and both active and inactive chlorine dioxides caused significantly higher reduction of >7.5 log CFU/ml in samples, compared to other tested sanitizers. The lowest reduction was obtained after disinfection with hypochlorite detergents. As expected, as doses and time of action increase, there was a significant reduction of the overall counts of P. salmonis. However, at lowest doses, only use of paracetic acids resulted in zero counts. Implementation of effective protocols, making use of adequate disinfectants, may enhance biosecurity, and ultimately, mitigate the impact of P. salmonis in farmed salmon. Copyright © 2018. Published by Elsevier B.V.

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

PubMed Central

Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

PubMed

Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

2011-05-01

Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

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

Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less

Ethanol inhibits human bone cell proliferation and function in vitro

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

Friday, K.E.; Howard, G.A.

1991-06-01

The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantlymore » reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.« less

New mechanistically based model for predicting reduction of biosolids waste by ozonation of return activated sludge.

PubMed

Isazadeh, Siavash; Feng, Min; Urbina Rivas, Luis Enrique; Frigon, Dominic

2014-04-15

Two pilot-scale activated sludge reactors were operated for 98 days to provide the necessary data to develop and validate a new mathematical model predicting the reduction of biosolids production by ozonation of the return activated sludge (RAS). Three ozone doses were tested during the study. In addition to the pilot-scale study, laboratory-scale experiments were conducted with mixed liquor suspended solids and with pure cultures to parameterize the biomass inactivation process during exposure to ozone. The experiments revealed that biomass inactivation occurred even at the lowest doses, but that it was not associated with extensive COD solubilization. For validation, the model was used to simulate the temporal dynamics of the pilot-scale operational data. Increasing the description accuracy of the inactivation process improved the precision of the model in predicting the operational data. Copyright © 2014 Elsevier B.V. All rights reserved.

DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.

EPA Science Inventory

The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

Evaluation of a ruminally dosed tall fescue seed extract as a model for fescue toxicosis in steers

USDA-ARS?s Scientific Manuscript database

Tall fescue (Lolium arundinaceum) toxicosis research is often complicated by a reduction in intake of infected forage or seed making treatment comparisons difficult. This study was conducted to develop a fescue toxicosis model that would allow for variations in DM intake without altering the quanti...

An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

PubMed

Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

2018-05-10

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

CT-guided brachytherapy of prostate cancer: reduction of effective dose from X-ray examination

NASA Astrophysics Data System (ADS)

Sanin, Dmitriy B.; Biryukov, Vitaliy A.; Rusetskiy, Sergey S.; Sviridov, Pavel V.; Volodina, Tatiana V.

2014-03-01

Computed tomography (CT) is one of the most effective and informative diagnostic method. Though the number of CT scans among all radiographic procedures in the USA and European countries is 11% and 4% respectively, CT makes the highest contribution to the collective effective dose from all radiographic procedures, it is 67% in the USA and 40% in European countries [1-5]. Therefore it is necessary to understand the significance of dose value from CT imaging to a patient . Though CT dose from multiple scans and potential risk is of great concern in pediatric patients, this applies to adults as well. In this connection it is very important to develop optimal approaches to dose reduction and optimization of CT examination. International Commission on Radiological Protection (ICRP) in its publications recommends radiologists to be aware that often CT image quality is higher than it is necessary for diagnostic confidence[6], and there is a potential to reduce the dose which patient gets from CT examination [7]. In recent years many procedures, such as minimally invasive surgery, biopsy, brachytherapy and different types of ablation are carried out under guidance of computed tomography [6;7], and during a procedures multiple CT scans focusing on a specific anatomic region are performed. At the Clinics of MRRC different types of treatment for patients with prostate cancer are used, incuding conformal CT-guided brachytherapy, implantation of microsources of I into the gland under guidance of spiral CT [8]. So, the purpose of the study is to choose optimal method to reduce radiation dose from CT during CT-guided prostate brachytherapy and to obtain the image of desired quality.

Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by split-dose thallium-dipyridamole myocardial scintigraphy

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

Koga, Y.; Yamaguchi, R.; Ogata, M.

1990-05-01

Split-dose thallium-dipyridamole myocardial scintigraphy was performed in patients with nonobstructive hypertrophic cardiomyopathy (HC) who had angiographically normal coronary arteries. The dipyridamole-induced increases in thallium-201 uptake, calculated to evaluate coronary vasodilatory capacity, were significantly lower in 30 patients with HC than in 13 control subjects (177 +/- 58 vs 281 +/- 46%) and the reductions were observed in both the septal and lateral segments. The reductions of the septal segment in HC patients were significantly greater than those in 10 hypertensive patients with comparable degrees of septal hypertrophy. Of patients with HC, 16 had increases in thallium uptake well below themore » normal range. Compared with those having normal increases, these patients had significantly lower exercise duration (11 vs 15 minutes), with 33% having ST depression develop at a workload less than or equal to 80 watts. These data indicate that approximately one-half of patients with HC have impaired coronary vasodilatory capacity that could be an important pathophysiologic abnormality of HC resulting in the development of myocardial ischemia and the impairment of cardiac performance during exercise.« less

Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation

PubMed Central

Sun, Wenjuan; JIA, Xianghong; XIE, Tianwu; XU, Feng; LIU, Qian

2013-01-01

With the rapid development of China's space industry, the importance of radiation protection is increasingly prominent. To provide relevant dose data, we first developed the Visible Chinese Human adult Female (VCH-F) phantom, and performed further modifications to generate the VCH-F Astronaut (VCH-FA) phantom, incorporating statistical body characteristics data from the first batch of Chinese female astronauts as well as reference organ mass data from the International Commission on Radiological Protection (ICRP; both within 1% relative error). Based on cryosection images, the original phantom was constructed via Non-Uniform Rational B-Spline (NURBS) boundary surfaces to strengthen the deformability for fitting the body parameters of Chinese female astronauts. The VCH-FA phantom was voxelized at a resolution of 2 × 2 × 4 mm3for radioactive particle transport simulations from isotropic protons with energies of 5000–10 000 MeV in Monte Carlo N-Particle eXtended (MCNPX) code. To investigate discrepancies caused by anatomical variations and other factors, the obtained doses were compared with corresponding values from other phantoms and sex-averaged doses. Dose differences were observed among phantom calculation results, especially for effective dose with low-energy protons. Local skin thickness shifts the breast dose curve toward high energy, but has little impact on inner organs. Under a shielding layer, organ dose reduction is greater for skin than for other organs. The calculated skin dose per day closely approximates measurement data obtained in low-Earth orbit (LEO). PMID:23135158

Effectiveness of a direct-to-consumer written health education program in the reduction of benzodiazepine and sedative-hypnotic use in an elderly population at a single Veterans Affairs medical center

PubMed Central

2018-01-01

Introduction: The use of benzodiazepines and sedative-hypnotics in the elderly is associated with a significant risk of delirium, falls, fractures, cognitive impairment, and motor vehicle accidents. This quality improvement project applies a direct-to-consumer intervention to an elderly veteran population to reduce the use of these medications. Methods: Patients aged 75 and older currently taking a benzodiazepine and/or a sedative-hypnotic were included in the project. Direct-to-consumer education intervention letters were mailed to patients within 30 days of their next appointment. Their providers were emailed a questionnaire after the patient's appointment. Providers were asked if the letter prompted a conversation regarding medication use, whether the provider initiated discussion regarding a taper, and whether a specific taper plan was developed. Medical records were reviewed to determine if a reduction in dose or discontinuation occurred. Results: Fifty-nine direct-to-consumer education letters were mailed to the patients. Follow-up questionnaires were e-mailed to 44 providers, and 27 providers responded. Twenty-two percent of patients had their benzodiazepine and/or sedative hypnotic dose reduced or discontinued after their follow-up appointment. Sixty-seven percent of veterans initiated a conversation with their provider regarding their medication with 74% of providers discussing dose reduction. Fifty-six percent of recipients developed a specific taper plan with their provider. Discussion: The data from this project suggests that direct-to-consumer patient education can reduce the exposure to benzodiazepines and sedative-hypnotics in an elderly veteran population. More data is needed on larger populations to further explore the benefit of direct-to-consumer interventions.

Optimal field-splitting algorithm in intensity-modulated radiotherapy: Evaluations using head-and-neck and female pelvic IMRT cases

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

Dou, Xin; Kim, Yusung, E-mail: yusung-kim@uiowa.edu; Bayouth, John E.

2013-04-01

To develop an optimal field-splitting algorithm of minimal complexity and verify the algorithm using head-and-neck (H and N) and female pelvic intensity-modulated radiotherapy (IMRT) cases. An optimal field-splitting algorithm was developed in which a large intensity map (IM) was split into multiple sub-IMs (≥2). The algorithm reduced the total complexity by minimizing the monitor units (MU) delivered and segment number of each sub-IM. The algorithm was verified through comparison studies with the algorithm as used in a commercial treatment planning system. Seven IMRT, H and N, and female pelvic cancer cases (54 IMs) were analyzed by MU, segment numbers, andmore » dose distributions. The optimal field-splitting algorithm was found to reduce both total MU and the total number of segments. We found on average a 7.9 ± 11.8% and 9.6 ± 18.2% reduction in MU and segment numbers for H and N IMRT cases with an 11.9 ± 17.4% and 11.1 ± 13.7% reduction for female pelvic cases. The overall percent (absolute) reduction in the numbers of MU and segments were found to be on average −9.7 ± 14.6% (−15 ± 25 MU) and −10.3 ± 16.3% (−3 ± 5), respectively. In addition, all dose distributions from the optimal field-splitting method showed improved dose distributions. The optimal field-splitting algorithm shows considerable improvements in both total MU and total segment number. The algorithm is expected to be beneficial for the radiotherapy treatment of large-field IMRT.« less

Impact on dose and image quality of a software-based scatter correction in mammography.

PubMed

Monserrat, Teresa; Prieto, Elena; Barbés, Benigno; Pina, Luis; Elizalde, Arlette; Fernández, Belén

2018-06-01

Background In 2014, Siemens developed a new software-based scatter correction (Progressive Reconstruction Intelligently Minimizing Exposure [PRIME]), enabling grid-less digital mammography. Purpose To compare doses and image quality between PRIME (grid-less) and standard (with anti-scatter grid) modes. Material and Methods Contrast-to-noise ratio (CNR) was measured for various polymethylmethacrylate (PMMA) thicknesses and dose values provided by the mammograph were recorded. CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQF inv ) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQF inv values in PRIME mode were lower for all thicknesses except for 40 mm of PMMA equivalent, in which IQF inv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts.

Head CT: Image quality improvement of posterior fossa and radiation dose reduction with ASiR - comparative studies of CT head examinations.

PubMed

Guziński, Maciej; Waszczuk, Łukasz; Sąsiadek, Marek J

2016-10-01

To evaluate head CT protocol developed to improve visibility of the brainstem and cerebellum, lower bone-related artefacts in the posterior fossa and maintain patient radioprotection. A paired comparison of head CT performed without Adaptive Statistical Iterative Reconstruction (ASiR) and a clinically indicated follow-up with 40 % ASiR was acquired in one group of 55 patients. Patients were scanned in the axial mode with different scanner settings for the brain and the posterior fossa. Objective image quality analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality analysis was based on brain structure visibility and evaluation of the artefacts. We achieved 19 % reduction of total DLP and significantly better image quality of posterior fossa structures. SNR for white and grey matter in the cerebellum were 34 % to 36 % higher, respectively, CNR was improved by 142 % and subjective analyses were better for images with ASiR. When imaging parameters are set independently for the brain and the posterior fossa imaging, ASiR has a great potential to improve CT performance: image quality of the brainstem and cerebellum is improved, and radiation dose for the brain as well as total radiation dose are reduced. •With ASiR it is possible to lower radiation dose or improve image quality •Sequentional imaging allows setting scan parameters for brain and posterior-fossa independently •We improved visibility of brainstem structures and decreased radiation dose •Total radiation dose (DLP) was decreased by 19.

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

PubMed Central

Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

2015-01-01

Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties. PMID:26713317

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

RADIATION PROTECTION CABIN FOR CATHETER-DIRECTED LIVER INTERVENTIONS: OPERATOR DOSE ASSESSMENT.

PubMed

Maleux, Geert; Bergans, Niki; Bosmans, Hilde; Bogaerts, Ria

2016-09-01

The number and complexity of interventional radiological procedures and in particular catheter-directed liver interventions have increased substantially. The current study investigates the reduction of personal doses when using a dedicated radiation protection cabin (RPC) for these procedures. Operator and assistant doses were assessed for 3 series of 20 chemoinfusion/chemoembolisation interventions, including an equal number of procedures with and without RPC. Whole body doses, finger doses and doses at the level of knees and eyes were evaluated with different types of TLD-100 Harshaw dosemeters. Dosemeters were also attached on the three walls of the RPC. The operator doses were significantly reduced by the RPC, but also without RPC, the doses appear to be limited as a result of thorough optimisation with existing radiation protection tools. The added value of the RPC should thus be determined by the outcome of balancing dose reduction and other aspects such as ergonomic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High Atomic Number Contrast Media Offer Potential for Radiation Dose Reduction in Contrast-Enhanced Computed Tomography.

PubMed

Roessler, Ann-Christin; Hupfer, Martin; Kolditz, Daniel; Jost, Gregor; Pietsch, Hubertus; Kalender, Willi A

2016-04-01

Spectral optimization of x-ray computed tomography (CT) has led to substantial radiation dose reduction in contrast-enhanced CT studies using standard iodinated contrast media. The purpose of this study was to analyze the potential for further dose reduction using high-atomic-number elements such as hafnium and tungsten. As in previous studies, spectra were determined for which the patient dose necessary to provide a given contrast-to-noise ratio (CNR) is minimized. We used 2 different quasi-anthropomorphic phantoms representing the liver cross-section of a normal adult and an obese adult patient with the lateral widths of 360 and 460 mm and anterior-posterior heights of 200 and 300 mm, respectively. We simulated and measured on 2 different scanners with x-ray spectra from 80 to 140 kV and from 70 to 150 kV, respectively. We determined the contrast for iodine-, hafnium-, and tungsten-based contrast media, the noise, and 3-dimensional dose distributions at all available tube voltages by measurements and by simulations. The dose-weighted CNR was determined as optimization parameter. Simulations and measurements were in good agreement regarding their dependence on energy for all parameters investigated. Hafnium provided the best performance for normal and for obese patient phantoms, indicating a dose reduction potential of 30% for normal and 50% for obese patients at 120 kV compared with iodine; this advantage increased further with higher kV values. Dose-weighted CNR values for tungsten were always slightly below the hafnium results. Iodine proved to be the superior choice at voltage values of 80 kV and below. Hafnium and tungsten both seem to be candidates for contrast-medium-enhanced CT of normal and obese adult patients with strongly reduced radiation dose at unimpaired image quality. Computed tomography examinations of obese patients will decrease in dose for higher kV values.

Capability of the nematode-trapping fungus Duddingtonia flagrans to reduce infective larvae of gastrointestinal nematodes in goat feces in the southeastern United States: dose titration and dose time interval studies.

PubMed

Terrill, T H; Larsen, M; Samples, O; Husted, S; Miller, J E; Kaplan, R M; Gelaye, S

2004-04-15

Infection with gastrointestinal nematodes, particularly Haemonchus contortus, is a major constraint to goat production in the southeastern United States. Non-anthelmintic control alternatives are needed due to increasing resistance of these nematodes to available anthelmintics. Two studies were completed in Central Georgia in August 1999, and April-May 2000, using Spanish does naturally infected with Haemonchus contortus, Trichostongylus colubriformis, and Cooperia spp. to evaluate effectiveness of nematode-trapping fungi as a biological control agent. In the first experiment, five levels of Duddingtonia flagrans spores were mixed with a complete diet and fed once daily to the does (three per treatment) in metabolism crates. The treatment concentrations were (1) 5 x 10(5), (2) 2.5 x 10(5), (3) 10(5), and (4) 5 x 10(4) spores per kilogram body weight (BW), and (5) no spores. Fungal spores were fed for the first 7 days of the 14-day trial, and fecal samples were collected daily from individual animals for analysis of fecal egg count and establishment of fecal cultures. Efficacy of the fungus at reducing development of infective larvae (L3) in the fecal cultures was evaluated. The mean reduction in L3 from day 2 of the treatment period until the day after treatment stopped (days 2-8) was 93.6, 80.2, 84.1, and 60.8% for animals given the highest to lowest spore doses, respectively. Within 3-6 days after termination of fungal spore feedings, reduction in L3 development was no longer apparent in any of the treated animals. In a second experiment, effectiveness of 2.5 x 10(5) spores of D. flagrans per kilogram BW fed to does every day, every second day, and every third day was evaluated. Reduction in L3 development by daily feeding was less in the second experiment than in the first experiment. Daily fungal spore feeding provided more consistent larval reduction than intermittant feeding (every second or third day). When fed daily under controlled conditions, D. flagrans was effective in significantly reducing development of L3 and appears to be an effective tool for biocontrol of parasitic nematodes in goats.

Computed tomography and patient risk: Facts, perceptions and uncertainties

PubMed Central

Power, Stephen P; Moloney, Fiachra; Twomey, Maria; James, Karl; O’Connor, Owen J; Maher, Michael M

2016-01-01

Since its introduction in the 1970s, computed tomography (CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses. PMID:28070242

Toward the development of a one-dose classical swine fever subunit vaccine: antigen titration, immunity onset, and duration of immunity

PubMed Central

Madera, Rachel F.; Wang, Lihua; Gong, Wenjie; Burakova, Yulia; Buist, Sterling; Nietfeld, Jerome; Henningson, Jamie; Cino-Ozuna, Ada G.; Tu, Changchun

2018-01-01

Highly contagious classical swine fever (CSF) remains a major trade and health problem in the pig industry, resulting in large economic losses worldwide. In CSF-endemic countries, attenuated CSF virus (CSFV) vaccines have been routinely used to control the disease. However, eradication of CSFV in a geographical area would require permanent reduction to zero presence of the virus. It is therefore of paramount importance to develop a safe, potent, and non-infectious CSF vaccine. We have previously reported on a cost-effective CSF E2 subunit vaccine, KNB-E2, which can protect against CSF symptoms in a single dose containing 75 µg of recombinant CSFV glycoprotein E2. In this study, we report on a series of animal studies undertaken to elucidate further the efficacy of KNB-E2. We found that pigs vaccinated with a single KNB-E2 dose containing 25 µg of recombinant CSFV glycoprotein E2 were protected from clinical symptoms of CSF. In addition, KNB-E2-mediated reduction of CSF symptoms was observed at two weeks post-vaccination and the vaccinated pigs continued to exhibit reduced CSF clinical signs when virus challenged at two months and four months post-vaccination. These results suggest that KNB-E2 effectively reduces CSF clinical signs, indicating the potential of this vaccine for safely minimizing CSF-related losses. PMID:29510474

SU-F-T-325: On the Use of Bolus in Dosimetry and Dose Reduction for Pacemaker and Defibrillator

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

Liu, W; Kenneth, R; Higgins, S

Purpose: Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is very large among CIEDs. Significant defects have been reported at dose as low as 0.15Gy. Failures causing discomfort have been reported at dose as low as 0.05Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2Gy limit. We investigate the use of bolus in in vivo dosimetry formore » CIEDs. Methods: In our clinic, high-energy beams (>10MV) are not used for patients with CIED due to neutron production. Solid water phantom measurements of out-of-field dose for a 6MV beam were performed using parallel plate chamber at different depth with and without 2cm bolus covering the chamber. In vivo dosimetry at skin surface above the pacemaker was performed with and without bolus for 3 patients with pacemaker <5cm from the field edge. Results: Chamber measured dose at depth ∼1 to 1.5cm below the skin surface, where the CIED is normally located, was reduced by ∼6% – 20% with bolus. The dose reduction became smaller at deeper depth. In vivo dosimetry at skin surface also yielded ∼20% – 60% lower dose when using bolus for the 3 patients. In general, TPS calculation underestimated the dose. The dose measured with bolus is closer to the dose at the depth of the pacemaker and less affected by contaminant electrons and linac head leakage. Conclusion: In vivo CIED dose measurements should be performed with 1 to 2cm bolus covering the dosimeter on the skin above the CIED for more accurate CIED dose estimation. The use of bolus also reduces the dose delivered to CIED.« less

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

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

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« less

Prediction of Warfarin Dose Reductions in Puerto Rican Patients, Based on Combinatorial CYP2C9 and VKORC1 Genotypes

PubMed Central

Valentin, Isa Ivette; Vazquez, Joan; Rivera-Miranda, Giselle; Seip, Richard L; Velez, Meredith; Kocherla, Mohan; Bogaard, Kali; Cruz-Gonzalez, Iadelisse; Cadilla, Carmen L; Renta, Jessica Y; Felliu, Juan F; Ramos, Alga S; Alejandro-Cowan, Yirelia; Gorowski, Krystyna; Ruaño, Gualberto; Duconge, Jorge

2012-01-01

BACKGROUND The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients. OBJECTIVE To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm. METHODS A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested. RESULTS Sixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients. CONCLUSIONS This study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA-guided warfarin dosing algorithm. PMID:22274142

Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes.

PubMed

Valentin, Isa Ivette; Vazquez, Joan; Rivera-Miranda, Giselle; Seip, Richard L; Velez, Meredith; Kocherla, Mohan; Bogaard, Kali; Cruz-Gonzalez, Iadelisse; Cadilla, Carmen L; Renta, Jessica Y; Feliu, Juan F; Ramos, Alga S; Alejandro-Cowan, Yirelia; Gorowski, Krystyna; Ruaño, Gualberto; Duconge, Jorge

2012-02-01

The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients. To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm. A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested. Sixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients. This study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA-guided warfarin dosing algorithm.

Comparative dosimetric and radiobiological assessment among a nonstandard RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecologic cancer

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

Pedicini, Piernicola, E-mail: ppiern@libero.it; Caivano, Rocchina; Fiorentino, Alba

2012-01-01

To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard (without vaginal applicator) RapidArc plans for 27 women with GC were developed to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were performed by means of dose-volume histogram and equivalent uniform dose (EUD) for planning target volume (PTV) and organs at risk (OARs). In addition, the integral dose and the overall treatment times were evaluated. RA, as well as IMRT, results in a high uniform dose onmore » PTV compared with HDR-BRT. However, the average of EUD for HDR-BRT was significantly higher than those with RA and IMRT. With respect to the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT. Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and better than HDR-BRT for the rectum because of a significant reduction of d{sub 2cc}, d{sub 1cc}, and d{sub max} (p < 0.01). Integral doses were always higher than HDR-BRT, although the values were very low. Delivery times were about the same and more than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion, the boost of dose on vaginal vault in patients affected by GC delivered by a nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT because of a reduction of delivery time and rectal dose at substantial comparable doses for the bladder and sigmoid. However HDR-BRT provides better performance in terms of PTV coverage as evidenced by a greater EUD.« less

Effects of Low-Dose Mindfulness-Based Stress Reduction (MBSR-ld) on Working Adults

ERIC Educational Resources Information Center

Klatt, Maryanna D.; Buckworth, Janet; Malarkey, William B.

2009-01-01

Mindfulness-based stress reduction (MBSR) has produced behavioral, psychological, and physiological benefits, but these programs typically require a substantial time commitment from the participants. This study assessed the effects of a shortened (low-dose [ld]) work-site MBSR intervention (MBSR-ld) on indicators of stress in healthy working…

Radiation dose reduction using a neck detection algorithm for single spiral brain and cervical spine CT acquisition in the trauma setting.

PubMed

Ardley, Nicholas D; Lau, Ken K; Buchan, Kevin

2013-12-01

Cervical spine injuries occur in 4-8 % of adults with head trauma. Dual acquisition technique has been traditionally used for the CT scanning of brain and cervical spine. The purpose of this study was to determine the efficacy of radiation dose reduction by using a single acquisition technique that incorporated both anatomical regions with a dedicated neck detection algorithm. Thirty trauma patients for brain and cervical spine CT were included and were scanned with the single acquisition technique. The radiation doses from the single CT acquisition technique with the neck detection algorithm, which allowed appropriate independent dose administration relevant to brain and cervical spine regions, were recorded. Comparison was made both to the doses calculated from the simulation of the traditional dual acquisitions with matching parameters, and to the doses of retrospective dual acquisition legacy technique with the same sample size. The mean simulated dose for the traditional dual acquisition technique was 3.99 mSv, comparable to the average dose of 4.2 mSv from 30 previous patients who had CT of brain and cervical spine as dual acquisitions. The mean dose from the single acquisition technique was 3.35 mSv, resulting in a 16 % overall dose reduction. The images from the single acquisition technique were of excellent diagnostic quality. The new single acquisition CT technique incorporating the neck detection algorithm for brain and cervical spine significantly reduces the overall radiation dose by eliminating the unavoidable overlapping range between 2 anatomical regions which occurs with the traditional dual acquisition technique.

Experimental benchmarking of a Monte Carlo dose simulation code for pediatric CT

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Yoshizumi, Terry; Colsher, James G.; Jones, Robert P.; Frush, Donald P.

2007-03-01

In recent years, there has been a desire to reduce CT radiation dose to children because of their susceptibility and prolonged risk for cancer induction. Concerns arise, however, as to the impact of dose reduction on image quality and thus potentially on diagnostic accuracy. To study the dose and image quality relationship, we are developing a simulation code to calculate organ dose in pediatric CT patients. To benchmark this code, a cylindrical phantom was built to represent a pediatric torso, which allows measurements of dose distributions from its center to its periphery. Dose distributions for axial CT scans were measured on a 64-slice multidetector CT (MDCT) scanner (GE Healthcare, Chalfont St. Giles, UK). The same measurements were simulated using a Monte Carlo code (PENELOPE, Universitat de Barcelona) with the applicable CT geometry including bowtie filter. The deviations between simulated and measured dose values were generally within 5%. To our knowledge, this work is one of the first attempts to compare measured radial dose distributions on a cylindrical phantom with Monte Carlo simulated results. It provides a simple and effective method for benchmarking organ dose simulation codes and demonstrates the potential of Monte Carlo simulation for investigating the relationship between dose and image quality for pediatric CT patients.

Generic radiation quarantine treatments: the next steps.

PubMed

Follett, Peter A

2009-08-01

In 2006, U.S. Department of Agriculture-Animal and Plant Health Inspection Service published a landmark rule providing generic radiation quarantine treatments. The rule approved radiation doses of 150 Gy for any tephritid fruit fly and 400 Gy for all other insects except the pupa and adult stages of Lepidoptera. The generic radiation treatments apply to all fresh horticultural commodities. Therefore, if a pest risk assessment demonstrates that no pupae or adult Lepidoptera are associated with a commodity, export approval can be forthcoming with no further research. Generic treatments are the culmination of decades of research but not an end point. Future research on quarantine and phytosanitary uses of radiation should focus on 1) development of specific doses for quarantine Lepidoptera not covered by the generic treatments, 2) reduction of dose levels for specific pests and commodities to shorten treatment time and minimize any deleterious effects of radiation treatment on commodity quality, 3) development of generic doses below 400 Gy for important groups of quarantine arthropods other than fruit flies, and 4) development of information on commodity tolerance and development of value-added irradiated fresh products that use generic radiation treatments. Generic treatments will facilitate safe trade between countries that have approved phytosanitary uses of radiation for fresh agricultural commodities.

Disinfection and reduction of organic load of sewage water by electron beam radiation

NASA Astrophysics Data System (ADS)

Maruthi, Y. Avasn; Das, N. Lakshmana; Hossain, Kaizar; Sarma, K. S. S.; Rawat, K. P.; Sabharwal, S.

2011-09-01

The efficacy of electron beam radiation for the disinfection and reduction of organic load of sewage water was assessed with ILU-6 Accelerator at Radiation Technology Development Division of the Bhabha Atomic Research Centre, Mumbai India. The current problem on environmental health in relation to water pollution insists for the safe disposal of sewage water. In general, sewage water comprises heterogeneous organic based chemicals as well as pathogens. EB treatment of the wastewater has found to be very effective in reducing the pathogens as well as organic load. EB dose of 1.5 kGy was sufficient for complete elimination of total coli forms. The experimental results elucidated the reduction of biological oxygen demand—BOD (35 and 51.7%) in both inlet and outlet sewage samples. Similarly reduction of chemical oxygen demand—COD was observed (37.54 and 52.32%) in both sewage samples with respect to increase in irradiation doses (0.45-6 kGy). The present study demonstrated the potential of ionizing radiation for disinfection of sewage and to increase the water quality of the wastewater by decreasing BOD and COD. So, the irradiation sewage water can find its application either in agriculture for irrigation, in industry for cooling purpose and some selected domestic purposes.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

PubMed

Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

2015-08-20

Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

Full dose reduction potential of statistical iterative reconstruction for head CT protocols in a predominantly pediatric population

PubMed Central

Mirro, Amy E.; Brady, Samuel L.; Kaufman, Robert. A.

2016-01-01

Purpose To implement the maximum level of statistical iterative reconstruction that can be used to establish dose-reduced head CT protocols in a primarily pediatric population. Methods Select head examinations (brain, orbits, sinus, maxilla and temporal bones) were investigated. Dose-reduced head protocols using an adaptive statistical iterative reconstruction (ASiR) were compared for image quality with the original filtered back projection (FBP) reconstructed protocols in phantom using the following metrics: image noise frequency (change in perceived appearance of noise texture), image noise magnitude, contrast-to-noise ratio (CNR), and spatial resolution. Dose reduction estimates were based on computed tomography dose index (CTDIvol) values. Patient CTDIvol and image noise magnitude were assessed in 737 pre and post dose reduced examinations. Results Image noise texture was acceptable up to 60% ASiR for Soft reconstruction kernel (at both 100 and 120 kVp), and up to 40% ASiR for Standard reconstruction kernel. Implementation of 40% and 60% ASiR led to an average reduction in CTDIvol of 43% for brain, 41% for orbits, 30% maxilla, 43% for sinus, and 42% for temporal bone protocols for patients between 1 month and 26 years, while maintaining an average noise magnitude difference of 0.1% (range: −3% to 5%), improving CNR of low contrast soft tissue targets, and improving spatial resolution of high contrast bony anatomy, as compared to FBP. Conclusion The methodology in this study demonstrates a methodology for maximizing patient dose reduction and maintaining image quality using statistical iterative reconstruction for a primarily pediatric population undergoing head CT examination. PMID:27056425

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

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

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

Prevalence of prescription opioid use disorder among chronic opioid therapy patients after health plan opioid dose and risk reduction initiatives.

PubMed

Von Korff, Michael; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Thakral, Manu; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha

2017-08-01

No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.

PubMed

Armenian, Saro H; Hudson, Melissa M; Chen, Ming Hui; Colan, Steven D; Lindenfeld, Lanie; Mills, George; Siyahian, Aida; Gelehrter, Sarah; Dang, Ha; Hein, Wendy; Green, Daniel M; Robison, Leslie L; Wong, F Lennie; Douglas, Pamela S; Bhatia, Smita

2016-10-04

Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population. The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosed <21 years of age), and previously treated with high-dose (≥300 mg/m 2 ) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability. When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF. ClinicalTrials.gov; NCT02717507.

[The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

PubMed

Leuker, G; Hingst, V

1992-10-01

Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

PubMed

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg.

PubMed

Vedder, Anouk C; Linthorst, Gabor E; Houge, Gunnar; Groener, Johannna E M; Ormel, Els E; Bouma, Berto J; Aerts, Johannes M F G; Hirth, Asle; Hollak, Carla E M

2007-07-11

Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial. Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54. Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease. International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534].

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

PubMed

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Molnár, László; McDermott, John; Zann, Vanessa; Church, Ann; Mair, Stuart; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-01

Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

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

Dial, Christian; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulatesmore » delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.« less

A Complier Average Causal Effect Analysis of the Stimulant Reduction Intervention using Dosed Exercise Study.

PubMed

Carmody, Thomas; Greer, Tracy L; Walker, Robrina; Rethorst, Chad D; Trivedi, Madhukar H

2018-06-01

Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years ( SD =11.1), and averaged 13.0 ( SD =9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-reported TimeLine Follow Back and urine drug screen results. The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41.0% vs. 55.7%, p <.01) and significantly lower days of stimulant use among those who relapsed (5.0 days vs. 9.9 days, p <.01). The CACE adjustment revealed significant, positive effects for exercise. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

PubMed Central

Häfner, D.; Beume, R.; Kilian, U.; Krasznai, G.; Lachmann, B.

1995-01-01

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 Figure 4 PMID:7582456

Dosimetric evaluation of intrafractional tumor motion by means of a robot driven phantom

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

Richter, Anne; Wilbert, Juergen; Flentje, Michael

2011-10-15

Purpose: The aim of the work was to investigate the influence of intrafractional tumor motion to the accumulated (absorbed) dose. The accumulated dose was determined by means of calculations and measurements with a robot driven motion phantom. Methods: Different motion scenarios and compensation techniques were realized in a phantom study to investigate the influence of motion on image acquisition, dose calculation, and dose measurement. The influence of motion on the accumulated dose was calculated by employing two methods (a model based and a voxel based method). Results: Tumor motion resulted in a blurring of steep dose gradients and a reductionmore » of dose at the periphery of the target. A systematic variation of motion parameters allowed the determination of the main influence parameters on the accumulated dose. The key parameters with the greatest influence on dose were the mean amplitude and the pattern of motion. Investigations on necessary safety margins to compensate for dose reduction have shown that smaller safety margins are sufficient, if the developed concept with optimized margins (OPT concept) was used instead of the standard internal target volume (ITV) concept. Both calculation methods were a reasonable approximation of the measured dose with the voxel based method being in better agreement with the measurements. Conclusions: Further evaluation of available systems and algorithms for dose accumulation are needed to create guidelines for the verification of the accumulated dose.« less

Post-focus expansion of ion beams for low fluence and large area MeV ion irradiation: Application to human brain tissue and electronics devices

NASA Astrophysics Data System (ADS)

Whitlow, Harry J.; Guibert, Edouard; Jeanneret, Patrick; Homsy, Alexandra; Roth, Joy; Krause, Sven; Roux, Adrien; Eggermann, Emmanuel; Stoppini, Luc

2017-08-01

Irradiation with ∼3 MeV proton fluences of 106-109 protons cm-2 have been applied to study the effects on human brain tissue corresponding to single-cell irradiation doses and doses received by electronic components in low-Earth orbit. The low fluence irradiations were carried out using a proton microbeam with the post-focus expansion of the beam; a method developed by the group of Breese [1]. It was found from electrophysiological measurements that the mean neuronal frequency of human brain tissue decreased to zero as the dose increased to 0-1050 Gy. Enhancement-mode MOSFET transistors exhibited a 10% reduction in threshold voltage for 2.7 MeV proton doses of 10 Gy while a NPN bipolar transistor required ∼800 Gy to reduce the hfe by 10%, which is consistent the expected values.

Implementation of a Community-Based Secondhand Smoke Reduction Intervention for Caregivers of Urban Children with Asthma: Process Evaluation, Successes and Challenges

ERIC Educational Resources Information Center

Blaakman, Susan; Tremblay, Paul J.; Halterman, Jill S.; Fagnano, Maria; Borrelli, Belinda

2013-01-01

Many children, including those with asthma, remain exposed to secondhand smoke. This manuscript evaluates the process of implementing a secondhand smoke reduction counseling intervention using motivational interviewing (MI) for caregivers of urban children with asthma, including reach, dose delivered, dose received and fidelity. Challenges,…

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

Dose perturbation effect of metallic spinal implants in proton beam therapy.

PubMed

Jia, Yingcui; Zhao, Li; Cheng, Chee-Wai; McDonald, Mark W; Das, Indra J

2015-09-08

The purpose of this study was to investigate the effect of dose perturbations for two metallic spinal screw implants in proton beam therapy in the perpendicular and parallel beam geometry. A 5.5 mm (diameter) by 45 mm (length) stainless steel (SS) screw and a 5.5 mm by 35 mm titanium (Ti) screw commonly used for spinal fixation were CT-scanned in a hybrid phantom of water and solid water. The CT data were processed with an orthopedic metal artifact reduction (O-MAR) algorithm. Treatment plans were generated for each metal screw with a proton beam oriented, first parallel and then perpendicular, to the longitudinal axis of the screw. The calculated dose profiles were compared with measured results from a plane-parallel ion chamber and Gafchromic EBT2 films. For the perpendicular setup, the measured dose immediately downstream from the screw exhibited dose enhancement up to 12% for SS and 8% for Ti, respectively, but such dose perturbation was not observed outside the lateral edges of the screws. The TPS showed 5% and 2% dose reductions immediately at the interface for the SS nd Ti screws, respectively, and up to 9% dose enhancements within 1 cm outside of the lateral edges of the screws. The measured dose enhancement was only observed within 5 mm from the interface along the beam path. At deeper depths, the lateral dose profiles appeared to be similar between the measurement and TPS, with dose reduction in the screw shadow region and dose enhancement within 1-2 cm outside of the lateral edges of the metals. For the parallel setup, no significant dose perturbation was detected at lateral distance beyond 3 mm away from both screws. Significant dose discrepancies exist between TPS calculations and ion chamber and film measurements in close proximity of high-Z inhomogeneities. The observed dose enhancement effect with proton therapy is not correctly modeled by TPS. An extra measure of caution should be taken when evaluating dosimetry with spinal metallic implants.

Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients.

PubMed

Yeaman, Fiona; Meek, Robert; Egerton-Warburton, Diana; Rosengarten, Pamela; Graudins, Andis

2014-06-01

There are currently no studies assessing effectiveness of sub-dissociative intranasal (IN) ketamine as the initial analgesic for adult patients in the ED. The study aims to examine the effectiveness of sub-dissociative IN ketamine as a primary analgesic agent for adult patients in the ED. This is a prospective, observational study of adult ED patients presenting with severe pain (≥6 on 11-point scale at triage). IN ketamine dose was 0.7 mg/kg, with secondary dose of 0.5 mg/kg at 15 min if pain did not improve. After 6 months, initial dose was increased to 1.0 mg/kg with the same optional secondary dose. The primary outcomes are change in VAS rating at 30 min; percentage of patients reporting clinically significant reduction in VAS (≥20 mm) at 30 min; dose resulting in clinically significant pain reduction. Of the 72 patients available for analysis, median age was 34.5 years and 64% were men. Median initial VAS rating was 76 mm (interquartile range [IQR]: 65-82). Median total dose of IN ketamine for all patients was 0.98 mg/kg (IQR: 0.75-1.15, range: 0.59-1.57). Median reduction in VAS rating at 30 min was 24 mm (IQR: 2-45). Forty (56%, 95% CI: 44.0-66.7) reported VAS reduction ≥20 mm, these patients having had a total median ketamine dose of 0.94 mg/kg (IQR: 0.72-1.04). IN ketamine, at a dose of about 1 mg/kg, was an effective analgesic agent in 56% of study patients. The place of IN ketamine in analgesic guidelines for adults requires further investigation. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

Reduction of radiation dose during facet joint injection using the new image guidance system SabreSource™: a prospective study in 60 patients

PubMed Central

Proschek, Dirk; Kafchitsas, K.; Rauschmann, M. A.; Kurth, A. A.; Vogl, T. J.

2008-01-01

Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource™. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4–L5 or L5–S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource™ system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51–69), body mass index (mean BMI 26.2, range 22.2–29.9) and preoperative pain (VAS 7.9, range 6–10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource™ system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource™ System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies). PMID:19082641

[BIOLOGICAL EFFECTIVENESS OF FISSION SPECTRUM NEUTRONS AND PROTONS WITH ENERGIES OF 60-126 MEV DURING ACUTE AND PROLONGED IRRADIATION].

PubMed

Shafirkin, A V

2015-01-01

Neutrons of the fission spectrum are characterized by relatively high values of linear energy transfer (LET). Data about their effects on biological objects are used to evaluate the risk of delayed effects of accelerated ions within the same LET range that serve as an experimental model of the nuclei component of galactic cosmic rays (GCR). Additionally, risks of delayed consequences to cosmonaut's health and average lifetime from certain GCR fluxes and secondary neutrons can be also prognosticated. The article deals with comparative analysis of the literature on reduction of average lifespan (ALS) of animals exposed to neutron reactor spectrum, 60-126 MeV protons, and X- and γ-rays in a broad range of radiation intensity and duration. It was shown that a minimal lifespan reduction by 5% occurs due to a brief exposure to neutrons with the absorbed dose of 5 cGy, whereas same lifespan reduction due to hard X- and γ-radiation occurs after absorption of a minimal dose of 100 cGy. Therefore, according to the estimated minimal ALS reduction in mice, neutron effectiveness is 20-fold higher. Biological effectiveness of protons as regards ALS reduction is virtually equal to that of standard types of radiation. Exposure to X- and γ-radiation with decreasing daily doses, and increasing number of fractions and duration gives rise to an apparent trend toward a less dramatic ALS reduction in mice; on the contrary, exposure to neutrons of varying duration had no effect on threshold doses for the specified ALS reductions. Factors of relative biological effectiveness of neutrons reached 40.

Evaluation of the radiation dose in the thyroid gland using different protective collars in panoramic imaging.

PubMed

Hafezi, Ladan; Arianezhad, S Marjan; Hosseini Pooya, Seyed Mahdi

2018-04-25

The value for the use of thyroid shield is one of the issues in radiation protection of patients in dental panoramic imaging. The objective of this research is to investigate the attenuation characteristics of some models of thyroid shielding in dental panoramic examinations. The effects of five different types of lead and lead-free (Pb-equivalent) shields on dose reduction of thyroid gland were investigated using implanted Thermoluminescence Dosemeters (TLDs) in head-neck parts of a Rando phantom. The results show that frontal lead and Pb-equivalent shields can reduce the thyroid dose around 50% and 19%, respectively. It can be concluded that the effective shielding area is an important parameter in thyroid gland dose reduction. Lead frontal collars with large effective shielding areas (>~300 cm 2 but not necessarily very large) are appropriate for an optimized thyroid gland dose reduction particularly for the critical patients in dental panoramic imaging. Regardless of the shape and thickness, using the Pb-equivalent shields is not justifiable in dental panoramic imaging.

A Monte Carlo study on quantifying the amount of dose reduction by shielding the superficial organs of an Iranian 11-year-old boy

PubMed Central

Akhlaghi, Parisa; Hoseinian-Azghadi, Elie; Miri-Hakimabad, Hashem; Rafat-Motavalli, Laleh

2016-01-01

A method for minimizing organ dose during computed tomography examinations is the use of shielding to protect superficial organs. There are some scientific reports that usage of shielding technique reduces the surface dose to patients with no appreciable loss in diagnostic quality. Therefore, in this Monte Carlo study based on the phantom of a 11-year-old Iranian boy, the effect of using an optimized shield on dose reduction to body organs was quantified. Based on the impact of shield on image quality, lead shields with thicknesses of 0.2 and 0.4 mm were considered for organs exposed directly and indirectly in the scan range, respectively. The results showed that there is 50%–62% reduction in amounts of dose for organs located fully or partly in the scan range at different tube voltages and modeling the true location of all organs in human anatomy, especially the ones located at the border of the scan, range affects the results up to 49%. PMID:28144117

TU-G-BRA-04: Changes in Regional Lung Function Measured by 4D-CT Ventilation Imaging for Thoracic Radiotherapy

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

Nakajima, Y; Kadoya, N; Kabus, S

Purpose: To test the hypothesis: 4D-CT ventilation imaging can show the known effects of radiotherapy on lung function: (1) radiation-induced ventilation reductions, and (2) ventilation increases caused by tumor regression. Methods: Repeat 4D-CT scans (pre-, mid- and/or post-treatment) were acquired prospectively for 11 thoracic cancer patients in an IRB-approved clinical trial. A ventilation image for each time point was created using deformable image registration and the Hounsfield unit (HU)-based or Jacobian-based metric. The 11 patients were divided into two subgroups based on tumor volume reduction using a threshold of 5 cm{sup 3}. To quantify radiation-induced ventilation reduction, six patients whomore » showed a small tumor volume reduction (<5 cm{sup 3}) were analyzed for dose-response relationships. To investigate ventilation increase caused by tumor regression, two of the other five patients were analyzed to compare ventilation changes in the lung lobes affected and unaffected by the tumor. The remaining three patients were excluded because there were no unaffected lobes. Results: Dose-dependent reductions of HU-based ventilation were observed in a majority of the patient-specific dose-response curves and in the population-based dose-response curve, whereas no clear relationship was seen for Jacobian-based ventilation. The post-treatment population-based dose-response curve of HU-based ventilation demonstrated the average ventilation reductions of 20.9±7.0% at 35–40 Gy (equivalent dose in 2-Gy fractions, EQD2), and 40.6±22.9% at 75–80 Gy EQD2. Remarkable ventilation increases in the affected lobes were observed for the two patients who showed an average tumor volume reduction of 37.1 cm{sup 3} and re-opening airways. The mid-treatment increase in HU-based ventilation of patient 3 was 100.4% in the affected lobes, which was considerably greater than 7.8% in the unaffected lobes. Conclusion: This study has demonstrated that 4D-CT ventilation imaging shows the known effects of radiotherapy on lung function: radiation-induced ventilation reduction and ventilation increase caused by tumor regression, providing validation for 4D-CT ventilation imaging. This study was supported in part by a National Lung Cancer Partnership Young Investigator Research grant.« less

Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

PubMed

Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

2015-12-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Azadirachtin: an effective systemic insecticide for control of Agrilus planipennis (Coleoptera: Buprestidae).

PubMed

McKenzie, Nicole; Helson, Blair; Thompson, Dean; Otis, Gard; McFarlane, John; Buscarini, Teresa; Meating, Joe

2010-06-01

The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), an invasive pest discovered in North America in 2002, is now well established and threatens ash (Fraxinus spp.) trees throughout the continent. Experiments were conducted to 1) examine the efficacy of an alternative natural pesticide, azadirachtin, to control emerald ash borer, and 2) determine foliar uptake and dissipation patterns after systemic injections of azadirachtin into trunks of small (2.2 cm diameter at breast height [dbh]), uninfested green ash trees. We found no evidence of mortality of adult beetles. In contrast, fewer larvae completed their development at dose levels > or = 1.7 mg (AI)/cm dbh and development ceased beyond the second instar at dose levels > or = 13.6 mg (AI)/cm dbh. Substantial concentrations (11.2 microg/g dry mass [SD = 7.55]) of azadirachtin were present in leaves within 7 d of treatment. After rapid initial uptake, concentrations in leaves declined logarithmically during the 55 d after injection. A similar pattern was observed in a separate experiment that examined the uptake and translocation of azadirachtin in larger green ash trees (22 cm dbh) treated with 250 mg (AI) /cm dbh with the EcoJect injection system. In another experiment, recently infested plantation green ash trees treated with doses > or = 40 mg (AI)/cm dbh had significant reductions in adult emergence approximately 1 yr postinjection. Given the inhibition of larval development, reduction of adult emergence, and the occurrence of foliar residues at biologically active concentrations, we conclude that azadirachtin is effective in protecting ash trees from emerald ash borer.

New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

PubMed

Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

2016-11-01

A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

PubMed

Salas, Ariel A; Smith, Kelly A; Rodgers, Mackenzie D; Phillips, Vivien; Ambalavanan, Namasivayam

2015-11-01

Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates. This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth. Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01). High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Radiation dose reduction with the adaptive statistical iterative reconstruction (ASIR) technique for chest CT in children: an intra-individual comparison.

PubMed

Lee, Seung Hyun; Kim, Myung-Joon; Yoon, Choon-Sik; Lee, Mi-Jung

2012-09-01

To retrospectively compare radiation dose and image quality of pediatric chest CT using a routine dose protocol reconstructed with filtered back projection (FBP) (the Routine study) and a low-dose protocol with 50% adaptive statistical iterative reconstruction (ASIR) (the ASIR study). We retrospectively reviewed chest CT performed in pediatric patients who underwent both the Routine study and the ASIR study on different days between January 2010 and August 2011. Volume CT dose indices (CTDIvol), dose length products (DLP), and effective doses were obtained to estimate radiation dose. The image quality was evaluated objectively as noise measured in the descending aorta and paraspinal muscle, and subjectively by three radiologists for noise, sharpness, artifacts, and diagnostic acceptability using a four-point scale. The paired Student's t-test and the Wilcoxon signed-rank test were used for statistical analysis. Twenty-six patients (M:F=13:13, mean age 11.7) were enrolled. The ASIR studies showed 60.3%, 56.2%, and 55.2% reductions in CTDIvol (from 18.73 to 7.43 mGy, P<0.001), DLP (from 307.42 to 134.51 mGy×cm, P<0.001), and effective dose (from 4.12 to 1.84 mSv, P<0.001), respectively, compared with the Routine studies. The objective noise was higher in the paraspinal muscle of the ASIR studies (20.81 vs. 16.67, P=0.004), but was not different in the aorta (18.23 vs. 18.72, P=0.726). The subjective image quality demonstrated no difference between the two studies. A low-dose protocol with 50% ASIR allows radiation dose reduction in pediatric chest CT by more than 55% while maintaining image quality. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

PubMed

Stocker, Gertraud; Hacker, Ulrich T; Fiteni, Frédéric; John Mahachie, Jestinah; Roth, Arnaud D; Van Cutsem, Eric; Peeters, Marc; Lordick, Florian; Mauer, Murielle

2018-06-12

Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m 2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m 2 , and 5.3% had both a BMI ≥ 30 kg/m 2 and a body surface area (BSA) ≥2 m 2 . Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m 2 and 32.4% with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , respectively. In patients with BMI ≥ 30 kg/m 2 , multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

PubMed

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism

PubMed Central

Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-01

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. PMID:26762348

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism.

PubMed

Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-13

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. 2016 BMJ Publishing Group Ltd.

The Safety, Effectiveness and Concentrations of Adjusted Lopinavir/Ritonavir in HIV-Infected Adults on Rifampicin-Based Antitubercular Therapy

PubMed Central

Decloedt, Eric H.; Maartens, Gary; Smith, Peter; Merry, Concepta; Bango, Funeka; McIlleron, Helen

2012-01-01

Objective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. Methods Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. Results 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1–9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. Conclusion Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate. PMID:22412856

Joint minimization of uplink and downlink whole-body exposure dose in indoor wireless networks.

PubMed

Plets, D; Joseph, W; Vanhecke, K; Vermeeren, G; Wiart, J; Aerts, S; Varsier, N; Martens, L

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.

Joint Minimization of Uplink and Downlink Whole-Body Exposure Dose in Indoor Wireless Networks

PubMed Central

Plets, D.; Joseph, W.; Vanhecke, K.; Vermeeren, G.; Wiart, J.; Aerts, S.; Varsier, N.; Martens, L.

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism. PMID:25793213

ALARA at nuclear power plants

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

Baum, J.W.

1990-01-01

Implementation of the As Low As Reasonably Achievable (ALARA) principle at nuclear power plants presents a continuing challenge for health physicists at utility corporate and plant levels, for plant designers, and for regulatory agencies. The relatively large collective doses at some plants are being addressed though a variety of dose reduction techniques. It is planned that this report will include material on historical aspects, management, valuation of dose reduction, quantitative and qualitative aspects of optimization, design, operational considerations, and training. The status of this work is summarized in this report. 30 refs., 1 fig., 6 tabs.

Radiation Dose Reduction by Indication-Directed Focused z-Direction Coverage for Neck CT.

PubMed

Parikh, A K; Shah, C C

2016-06-01

The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose-length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management. © 2016 by American Journal of Neuroradiology.

CT of the chest with model-based, fully iterative reconstruction: comparison with adaptive statistical iterative reconstruction.

PubMed

Ichikawa, Yasutaka; Kitagawa, Kakuya; Nagasawa, Naoki; Murashima, Shuichi; Sakuma, Hajime

2013-08-09

The recently developed model-based iterative reconstruction (MBIR) enables significant reduction of image noise and artifacts, compared with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP). The purpose of this study was to evaluate lesion detectability of low-dose chest computed tomography (CT) with MBIR in comparison with ASIR and FBP. Chest CT was acquired with 64-slice CT (Discovery CT750HD) with standard-dose (5.7 ± 2.3 mSv) and low-dose (1.6 ± 0.8 mSv) conditions in 55 patients (aged 72 ± 7 years) who were suspected of lung disease on chest radiograms. Low-dose CT images were reconstructed with MBIR, ASIR 50% and FBP, and standard-dose CT images were reconstructed with FBP, using a reconstructed slice thickness of 0.625 mm. Two observers evaluated the image quality of abnormal lung and mediastinal structures on a 5-point scale (Score 5 = excellent and score 1 = non-diagnostic). The objective image noise was also measured as the standard deviation of CT intensity in the descending aorta. The image quality score of enlarged mediastinal lymph nodes on low-dose MBIR CT (4.7 ± 0.5) was significantly improved in comparison with low-dose FBP and ASIR CT (3.0 ± 0.5, p = 0.004; 4.0 ± 0.5, p = 0.02, respectively), and was nearly identical to the score of standard-dose FBP image (4.8 ± 0.4, p = 0.66). Concerning decreased lung attenuation (bulla, emphysema, or cyst), the image quality score on low-dose MBIR CT (4.9 ± 0.2) was slightly better compared to low-dose FBP and ASIR CT (4.5 ± 0.6, p = 0.01; 4.6 ± 0.5, p = 0.01, respectively). There were no significant differences in image quality scores of visualization of consolidation or mass, ground-glass attenuation, or reticular opacity among low- and standard-dose CT series. Image noise with low-dose MBIR CT (11.6 ± 1.0 Hounsfield units (HU)) were significantly lower than with low-dose ASIR (21.1 ± 2.6 HU, p < 0.0005), low-dose FBP CT (30.9 ± 3.9 HU, p < 0.0005), and standard-dose FBP CT (16.6 ± 2.3 HU, p < 0.0005). MBIR shows greater potential than ASIR for providing diagnostically acceptable low-dose CT without compromising image quality. With radiation dose reduction of >70%, MBIR can provide equivalent lesion detectability of standard-dose FBP CT.

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

PubMed Central

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple Emax model with a fixed E0, which provided a common Emax and an approximate twofold difference in ED50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries. PMID:21151159

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients.

PubMed

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E(max) model with a fixed E(0), which provided a common E(max) and an approximate twofold difference in ED(50) for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.

Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody.

PubMed

Syvänen, Stina; Hultqvist, Greta; Gustavsson, Tobias; Gumucio, Astrid; Laudon, Hanna; Söderberg, Linda; Ingelsson, Martin; Lannfelt, Lars; Sehlin, Dag

2018-05-24

Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed Aβ protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble Aβ protofibrils. Aβ protein precursor (AβPP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFv8D3), in comparison with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158). Soluble Aβ protofibrils and total Aβ in the brain were measured by enzyme-linked immunosorbent assay (ELISA). Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoradiography. ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble Aβ protofibrils in both RmAb158-scFv8D3- and high-dose RmAb158-treated mice, whereas there was no Aβ protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed different brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect Aβ levels by different mechanisms. With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood-brain barrier can be used to increase the efficacy of Aβ immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs.

Characterization of a commercial hybrid iterative and model-based reconstruction algorithm in radiation oncology

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

Price, Ryan G.; Vance, Sean; Cattaneo, Richard

2014-08-15

Purpose: Iterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning. Methods: CT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25–800 mAs. IR was applied at levels corresponding to noise reduction of 0.89–0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generatedmore » over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF{sub task}) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified. Results: NPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼0.1 mm{sup −1}) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼13 HU for bone (∼1% difference)]. For uniformity, differences were ∼1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTF{sub task} decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p < 0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [−1.2 ± 4.9 HU (range: −17.6–12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with <2% difference in intensity from FBP combined with aggressive IRL6. Conclusions: These results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.« less

Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

PubMed Central

Colbert, Nathan K.W.; Pelletier, Nicole C.; Cote, Joyce M.; Concannon, John B.; Jurdak, Nicole A.; Minott, Sara B.; Markowski, Vincent P.

2005-01-01

In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs. PMID:15929892

Radiation-Induced Noncancer Risks in Interventional Cardiology: Optimisation of Procedures and Staff and Patient Dose Reduction

PubMed Central

Khairuddin Md Yusof, Ahmad

2013-01-01

Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768

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

Grande, T.; Bueren, J.A.

We have investigated whether a relatively low dose of 500 mGy of X rays given as a single acute irradiation at different stages of pre-and postnatal development induces significant changes in the content of femoral hematopoietic progenitores during a 1-year period after irradiation. Data obtained show that, in the case of 4-day-old embryos as well as in 2-day, 8-day and 12-week-old mice, this dose is below the threshold capable of inducing a long-term impairment of hematopoiesis in the mouse. Nevertheless, in mice irradiated at the 13th or the 17th day postconception, a hematopoietic dysfunction consisting of a significant reduction inmore » the proportion of femoral granulocyte-macrophage colony-forming units (CFU-GM) was manifested 1 year after irradiation. Our study confirms that, for most stages of development in the mouse, a single acute X irradiation of 500 mGy is below the threshold dose capable of inducing deterministic effects in the mouse hematopoietic system, although it reveals the induction of a significant impairment in the CFU-GM population when irradiation is given at the late stages of embryonic development. 24 refs., 4 figs.« less

Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?

PubMed

Nesvacil, Nicole; Tanderup, Kari; Lindegaard, Jacob C; Pötter, Richard; Kirisits, Christian

2016-09-01

The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves. A dose-response simulation study was based on systematic and random dose uncertainties and TCP/NTCP models for CTV and rectum. Large patient cohorts were simulated assuming different levels of dosimetric uncertainties. TCP and NTCP were computed, based on the planned doses, the simulated dose uncertainty, and an underlying TCP/NTCP model. Systematic uncertainties of 3-20% and random uncertainties with a 5-30% standard deviation per BT fraction were analysed. Systematic dose uncertainties of 5% lead to a 1% decrease/increase of TCP/NTCP, while random uncertainties of 10% had negligible impact on the dose-response curve at clinically relevant dose levels for target and OAR. Random OAR dose uncertainties of 30% resulted in an NTCP increase of 3-4% for planned doses of 70-80Gy EQD2. TCP is robust to dosimetric uncertainties when dose prescription is in the more flat region of the dose-response curve at doses >75Gy. For OARs, improved clinical outcome is expected by reduction of uncertainties via sophisticated dose delivery and treatment verification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

None

Purpose of the meeting was to provide a record of experience at nuclear facilities, other than TMI-2, of events and incidents which have required decontamination and dose reduction activities, and to furnish GPU and others involved in the TMI-2 cleanup with the results of that decontamination and dose reduction technology. Separate abstracts were prepared for 24 of the 25 papers; the remaining paper had been previously abstracted. (DLC)

MO-DE-204-01: Radiation Doses in Over 50 Developing Countries of Asia, Africa, Eastern European and Latin America

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

Rehani, M.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Traditional and MLC based dose compensator design for patients with hip prostheses undergoing pelvic radiation therapy.

PubMed

Alecu, R; Alecu, M; Loomis, T; Ochran, T; He, T

1999-01-01

Perturbations in the dose distribution caused by a hip prosthesis when treating pelvic malignancies can result in unacceptable dose inhomogeneities within the target volume. Our results, obtained by in vivo exit dose measurements with diodes, showed a 55% reduction in the dose at the exit dmax of a lateral 15 MV photon beam after passing through a bilateral cobalt-chrome alloy hip prosthesis. Such an inhomogeneous dose distribution may decrease the curability. Solutions such as treatment techniques to avoid the prosthesis are often not the best choice as the dose to the rectum may be unacceptably high. In this work an alternative method of dose compensator is presented. Two types of dose compensators were designed based on a 3-D treatment planning system and CT images of a pelvic phantom containing a hip prosthesis: one was fabricated from a polyethylene-lead slab in the representation of step fringes and placed on a tray in the path of the beam while the other was produced by the use of several fields shaped with a multileaf collimator. The calculation procedures developed by the authors for generating the compensators are described. Results of film measurements performed in a phantom with and without the compensators in place are discussed.

Sterility and Sexual Competitiveness of Tapachula-7 Anastrepha ludens Males Irradiated at Different Doses.

PubMed

Orozco-Dávila, Dina; Adriano-Anaya, Maria de Lourdes; Quintero-Fong, Luis; Salvador-Figueroa, Miguel

2015-01-01

A genetic sexing strain of Anastrepha ludens (Loew), Tapachula-7, was developed by the Mexican Program Against Fruit Flies to produce and release only males in programs where the sterile insect technique (SIT) is applied. Currently, breeding are found at a massive scale, and it is necessary to determine the optimum irradiation dose that releases sterile males with minimum damage to their sexual competitiveness. Under laboratory and field conditions, we evaluated the effects of gamma irradiation at doses of 0, 20, 40, 60 and 80 Gy on the sexual competitiveness of males, the induction of sterility in wild females and offspring survivorship. The results of the study indicate that irradiation doses have a significant effect on the sexual behavior of males. A reduction of mating capacity was inversely proportional to the irradiation dose of males. It is estimated that a dose of 60 Gy can induce more than 99% sterility in wild females. In all treatments, the degree of offspring fertility was correlated with the irradiation dose of the parents. In conclusion, the results of the study indicate that a dose of 60 Gy can be applied in sterile insect technique release programs. The application of this dose in the new genetic sexing strain of A. ludens is discussed.

Sterility and Sexual Competitiveness of Tapachula-7 Anastrepha ludens Males Irradiated at Different Doses

PubMed Central

Orozco-Dávila, Dina; Adriano-Anaya, Maria de Lourdes; Quintero-Fong, Luis; Salvador-Figueroa, Miguel

2015-01-01

A genetic sexing strain of Anastrepha ludens (Loew), Tapachula-7, was developed by the Mexican Program Against Fruit Flies to produce and release only males in programs where the sterile insect technique (SIT) is applied. Currently, breeding are found at a massive scale, and it is necessary to determine the optimum irradiation dose that releases sterile males with minimum damage to their sexual competitiveness. Under laboratory and field conditions, we evaluated the effects of gamma irradiation at doses of 0, 20, 40, 60 and 80 Gy on the sexual competitiveness of males, the induction of sterility in wild females and offspring survivorship. The results of the study indicate that irradiation doses have a significant effect on the sexual behavior of males. A reduction of mating capacity was inversely proportional to the irradiation dose of males. It is estimated that a dose of 60 Gy can induce more than 99% sterility in wild females. In all treatments, the degree of offspring fertility was correlated with the irradiation dose of the parents. In conclusion, the results of the study indicate that a dose of 60 Gy can be applied in sterile insect technique release programs. The application of this dose in the new genetic sexing strain of A. ludens is discussed. PMID:26274926

[SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

PubMed

Ushakov, I B; Grigoriev, Yu G; Shafirkin, A V; Shurshakov, V A

2016-01-01

Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

Effect of a single prophylactic preoperative oral antibiotic dose on surgical site infection following complex dermatological procedures on the nose and ear: a prospective, randomised, controlled, double-blinded trial.

PubMed

Rosengren, Helena; Heal, Clare F; Buttner, Petra G

2018-04-19

There is limited published research studying the effect of antibiotic prophylaxis on surgical site infection (SSI) in dermatological surgery, and there is no consensus for its use in higher-risk cases. The objective of this study was to determine the effectiveness of a single oral preoperative 2 g dose of cephalexin in preventing SSI following flap and graft dermatological closures on the nose and ear. Prospective double-blinded, randomised, placebo-controlled trial testing for difference in infection rates. Primary care skin cancer clinics in North Queensland, Australia, were randomised to 2 g oral cephalexin or placebo 40-60 min prior to skin incision. 154 consecutive eligible patients booked for flap or graft closure following skin cancer excision on the ear and nose. 2 g dose of cephalexin administered 40-60 min prior to surgery. Overall 8/69 (11.6%) controls and 1/73 (1.4%) in the intervention group developed SSI (p=0.015; absolute SSI reduction 10.2%; number needed to treat (NNT) for benefit 9.8, 95% CI 5.5 to 45.5). In males, 7/44 controls and 0/33 in the intervention group developed SSI (p=0.018; absolute SSI reduction 15.9%; NNT for benefit 6.3, 95% CI 3.8 to 19.2). SSI was much lower in female controls (1/25) and antibiotic prophylaxis did not further reduce this (p=1.0). There was no difference between the study groups in adverse symptoms attributable to high-dose antibiotic administration (p=0.871). A single oral 2 g dose of cephalexin given before complex skin closure on the nose and ear reduced SSI. ANZCTR 365115; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice1

PubMed Central

Kojima, Fumiaki; Kapoor, Mohit; Yang, Lihua; Fleishaker, Erica L.; Ward, Martin R.; Monrad, Seetha U.; Kottangada, Ponnappa C.; Pace, Charles Q.; Clark, James A.; Woodward, Jerold G.; Crofford, Leslie J.

2008-01-01

Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH2 to PGE2. The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen (CII), including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. PMID:18523303

Dose reduction in 64-row whole-body CT in multiple trauma: an optimized CT protocol with iterative image reconstruction on a gemstone-based scintillator.

PubMed

Geyer, Lucas L; Körner, Markus; Harrieder, Andreas; Mueck, Fabian G; Deak, Zsuzsanna; Wirth, Stefan; Linsenmaier, Ulrich

2016-01-01

Evaluation of potential dose savings by implementing adaptive statistical iterative reconstruction (ASiR) on a gemstone-based scintillator in a clinical 64-row whole-body CT (WBCT) protocol after multiple trauma. Dose reports of 152 WBCT scans were analysed for two 64-row multidetector CT scanners (Scanners A and B); the main scanning parameters were kept constant. ASiR and a gemstone-based scintillator were used in Scanner B, and the noise index was adjusted (head: 5.2 vs 6.0; thorax/abdomen: 29.0 vs 46.0). The scan length, CT dose index (CTDI) and dose-length product (DLP) were analysed. The estimated mean effective dose was calculated using normalized conversion factors. Student's t-test was used for statistics. Both the mean CTDI (mGy) (Scanner A: 53.8 ± 2.0, 10.3 ± 2.5, 14.4 ± 3.7; Scanner B: 48.7 ± 2.2, 7.1 ± 2.3, 9.1 ± 3.6; p < 0.001, respectively) and the mean DLP (mGy cm) (Scanner A: 1318.9 ± 167.8, 509.3 ± 134.7, 848.8 ± 254.0; Scanner B: 1190.6 ± 172.6, 354.6 ± 128.3, 561.0 ± 246.7; p < 0.001, respectively) for the head, thorax and abdomen were significantly reduced with Scanner B. There was no relevant difference in scan length. The total mean effective dose (mSv) was significantly decreased with Scanner B (24.4 ± 6.0, 17.2 ± 5.8; p < 0.001). The implementation of ASiR and a gemstone-based scintillator allows for significant dose savings in a clinical WBCT protocol. Recent technical developments can significantly reduce radiation dose of WBCT in multiple trauma. Dose reductions of 10-34% can be achieved.

Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus.

PubMed

Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Leung, Kenneth Mei Yee; Lee, Yong Sung; Lee, Jae-Seong

2014-07-01

Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus. Copyright © 2014 Elsevier B.V. All rights reserved.

WE-EF-207-05: Monte Carlo Dosimetry for a Dedicated Cone-Beam CT Head Scanner

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

Sisniega, A; Zbijewski, W; Xu, J

Purpose: Cone-Beam CT (CBCT) is an attractive platform for point-of-care imaging of traumatic brain injury and intracranial hemorrhage. This work implements and evaluates a fast Monte-Carlo (MC) dose estimation engine for development of a dedicated head CBCT scanner, optimization of acquisition protocols, geometry, bowtie filter designs, and patient-specific dosimetry. Methods: Dose scoring with a GPU-based MC CBCT simulator was validated on an imaging bench using a modified 16 cm CTDI phantom with 7 ion chamber shafts along the central ray for 80–100 kVp (+2 mm Al, +0.2 mm Cu). Dose distributions were computed in a segmented CBCT reconstruction of anmore » anthropomorphic head phantom with 4×10{sup 5} tracked photons per scan (5 min runtime). Circular orbits with angular span ranging from short scan (180° + fan angle) to full rotation (360°) were considered for fixed total mAs per scan. Two aluminum filters were investigated: aggressive bowtie, and moderate bowtie (matched to 16 cm and 32 cm water cylinder, respectively). Results: MC dose estimates showed strong agreement with measurements (RMSE<0.001 mGy/mAs). A moderate (aggressive) bowtie reduced the dose, per total mAs, by 20% (30%) at the center of the head, by 40% (50%) at the eye lens, and by 70% (80%) at the posterior skin entrance. For the no bowtie configuration, a short scan reduced the eye lens dose by 62% (from 0.08 mGy/mAs to 0.03 mGy/mAs) compared to full scan, although the dose to spinal bone marrow increased by 40%. For both bowties, the short scan resulted in a similar 40% increase in bone marrow dose, but the reduction in the eye lens was more pronounced: 70% (90%) for the moderate (aggressive) bowtie. Conclusions: Dose maps obtained with validated MC simulation demonstrated dose reduction in sensitive structures (eye lens and bone marrow) through combination of short-scan trajectories and bowtie filters. Xiaohui Wang and David Foos are employees of Carestream Health.« less

Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT.

PubMed

Wallace, Adam N; Vyhmeister, Ross; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; Ramirez-Giraldo, Juan Carlos; McKinstry, Robert C

2015-06-01

Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

PubMed

Sorenmo, Karin; Overley, B; Krick, E; Ferrara, T; LaBlanc, A; Shofer, F

2010-09-01

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-558: Assessing the Effect of Inter-Fractional Motion in Esophageal Sparing Plans.

PubMed

Williamson, R; Bluett, J; Niedzielski, J; Liao, Z; Gomez, D; Court, L

2012-06-01

To compare esophageal dose distributions in esophageal sparing IMRT plans with predicted dose distributions which include the effect of inter-fraction motion. Seven lung cancer patients were used, each with a standard and an esophageal sparing plan (74Gy, 2Gy fractions). The average max dose to esophagus was 8351cGy and 7758cGy for the standard and sparing plans, respectively. The average length of esophagus for which the total circumference was treated above 60Gy (LETT60) was 9.4cm in the standard plans and 5.8cm in the sparing plans. In order to simulate inter-fractional motion, a three-dimensional rigid shift was applied to the calculated dose field. A simulated course of treatment consisted of a single systematic shift applied throughout the treatment as well a random shift for each of the 37 fractions. Both systematic and random shifts were generated from Gaussian distributions of 3mm and 5mm standard deviation. Each treatment course was simulated 1000 times to obtain an expected distribution of the delivered dose. Simulated treatment dose received by the esophagus was less than dose seen in the treatment plan. The average reduction in maximum esophageal dose for the standard plans was 234cGy and 386cGY for the 3mm and 5mm Gaussian distributions, respectively. The average reduction in LETT60 was 0.6cm and 1.7cm, for the 3mm and 5mm distributions respectively. For the esophageal sparing plans, the average reduction in maximum esophageal dose was 94cGy and 202cGy for 3mm and 5mm Gaussian distributions, respectively. The average change in LETT60 for the esophageal sparing plans was smaller, at 0.1cm (increase) and 0.6cm (reduction), for the 3mm and 5mm distributions, respectively. Interfraction motion consistently reduced the maximum doses to the esophagus for both standard and esophageal sparing plans. © 2012 American Association of Physicists in Medicine.

New cardiac cameras: single-photon emission CT and PET.

PubMed

Slomka, Piotr J; Berman, Daniel S; Germano, Guido

2014-07-01

Nuclear cardiology instrumentation has evolved significantly in the recent years. Concerns about radiation dose and long acquisition times have propelled developments of dedicated high-efficiency cardiac SPECT scanners. Novel collimator designs, such as multipinhole or locally focusing collimators arranged in geometries that are optimized for cardiac imaging, have been implemented to enhance photon-detection sensitivity. Some of these new SPECT scanners use solid-state photon detectors instead of photomultipliers to improve image quality and to reduce the scanner footprint. These new SPECT devices allow dramatic up to 7-fold reduction in acquisition times or similar reduction in radiation dose. In addition, new hardware for photon attenuation correction allowing ultralow radiation doses has been offered by some vendors. To mitigate photon attenuation artifacts for the new SPECT scanners not equipped with attenuation correction hardware, 2-position (upright-supine or prone-supine) imaging has been proposed. PET hardware developments have been primarily driven by the requirements of oncologic imaging, but cardiac imaging can benefit from improved PET image quality and improved sensitivity of 3D systems. The time-of-flight reconstruction combined with resolution recovery techniques is now implemented by all major PET vendors. These new methods improve image contrast and image resolution and reduce image noise. High-sensitivity 3D PET without interplane septa allows reduced radiation dose for cardiac perfusion imaging. Simultaneous PET/MR hybrid system has been developed. Solid-state PET detectors with avalanche photodiodes or digital silicon photomultipliers have been introduced, and they offer improved imaging characteristics and reduced sensitivity to electromagnetic MR fields. Higher maximum count rate of the new PET detectors allows routine first-pass Rb-82 imaging, with 3D PET acquisition enabling clinical utilization of dynamic imaging with myocardial flow measurements for this tracer. The availability of high-end CT component in most PET/CT configurations enables hybrid multimodality cardiac imaging protocols with calcium scoring or CT angiography or both. Copyright © 2014. Published by Elsevier Inc.

Stacked competitive networks for noise reduction in low-dose CT

PubMed Central

Du, Wenchao; Chen, Hu; Wu, Zhihong; Sun, Huaiqiang; Liao, Peixi

2017-01-01

Since absorption of X-ray radiation has the possibility of inducing cancerous, genetic and other diseases to patients, researches usually attempt to reduce the radiation dose. However, reduction of the radiation dose associated with CT scans will unavoidably increase the severity of noise and artifacts, which can seriously affect diagnostic confidence. Due to the outstanding performance of deep neural networks in image processing, in this paper, we proposed a Stacked Competitive Network (SCN) approach to noise reduction, which stacks several successive Competitive Blocks (CB). The carefully handcrafted design of the competitive blocks was inspired by the idea of multi-scale processing and improvement the network’s capacity. Qualitative and quantitative evaluations demonstrate the competitive performance of the proposed method in noise suppression, structural preservation, and lesion detection. PMID:29267360

Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

PubMed

Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

2009-10-01

A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Effectiveness of the implementation of a simple radiation reduction protocol in the catheterization laboratory.

PubMed

Jurado-Román, Alfonso; Sánchez-Pérez, Ignacio; Lozano Ruíz-Poveda, Fernando; López-Lluva, María T; Pinilla-Echeverri, Natalia; Moreno Arciniegas, Andrea; Agudo-Quilez, Pilar; Gil Agudo, Antonio

2016-01-01

A reduction in radiation doses at the catheterization laboratory, maintaining the quality of procedures is essential. Our objective was to analyze the results of a simple radiation reduction protocol at a high-volume interventional cardiology unit. We analyzed 1160 consecutive procedures: 580 performed before the implementation of the protocol and 580 after it. The protocol consisted in: the reduction of the number of ventriculographies and aortographies, the optimization of the collimation and the geometry of the X ray tube-patient-receptor, the use of low dose-rate fluoroscopy and the reduction of the number of cine sequences using the software "last fluoroscopy hold". There were no significant differences in clinical baseline features or in the procedural characteristics with the exception of a higher percentage of radial approach (30.7% vs 69.6%; p<0.001) and of percutaneous coronary interventions of chronic total occlusions after the implementation of the protocol (2.1% vs 6.7%; p=0,001). Angiographic success was similar during both periods (98.3% vs 99.2%; p=0.2). There were no significant differences between both periods regarding the overall duration of the procedures (26.9 vs 29.6min; p=0.14), or the fluoroscopy time (13.3 vs 13.2min; p=0.8). We observed a reduction in the percentage of procedures with ventriculography (80.9% vs 7.1%; p<0.0001) or aortography (15.4% vs 4.4%; p<0.0001), the cine runs (21.8 vs 6.9; p<0.0001) and the dose-area product (165 vs 71 Gyxcm(2); p<0.0001). With the implementation of a simple radiation reduction protocol, a 57% reduction of dose-area product was observed without a reduction in the quality or the complexity of procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Reducing image noise in computed tomography (CT) colonography: effect of an integrated circuit CT detector.

PubMed

Liu, Yu; Leng, Shuai; Michalak, Gregory J; Vrieze, Thomas J; Duan, Xinhui; Qu, Mingliang; Shiung, Maria M; McCollough, Cynthia H; Fletcher, Joel G

2014-01-01

To investigate whether the integrated circuit (IC) detector results in reduced noise in computed tomography (CT) colonography (CTC). Three hundred sixty-six consecutive patients underwent clinically indicated CTC using the same CT scanner system, except for a difference in CT detectors (IC or conventional). Image noise, patient size, and scanner radiation output (volume CT dose index) were quantitatively compared between patient cohorts using each detector system, with separate comparisons for the abdomen and pelvis. For the abdomen and pelvis, despite significantly larger patient sizes in the IC detector cohort (both P < 0.001), image noise was significantly lower (both P < 0.001), whereas volume CT dose index was unchanged (both P > 0.18). Based on the observed image noise reduction, radiation dose could alternatively be reduced by approximately 20% to result in similar levels of image noise. Computed tomography colonography images acquired using the IC detector had significantly lower noise than images acquired using the conventional detector. This noise reduction can permit further radiation dose reduction in CTC.

Utilizing placebo mechanisms for dose reduction in pharmacotherapy.

PubMed

Doering, Bettina K; Rief, Winfried

2012-03-01

The knowledge and systematic application of the placebo effect remains limited, although its importance to the treatment of various medical conditions has increasingly been recognized. A possible application of the placebo effect to pharmacotherapy is seen in conditioning processes that aim at a placebo-controlled dose reduction of drugs while maintaining the efficacy of the medical treatment. The pairing of a placebo and a pharmacological agent may achieve satisfactory treatment outcomes in combination with a lower dose of medication. This procedure includes classic and instrumental conditioning processes that involve both conscious and non-conscious information processing. Although recent studies have gathered preliminary evidence for the efficacy of placebo-controlled dose reduction (e.g. in psoriasis and attention deficit hyperactivity disorder [ADHD]), they have also illustrated the difficulties that are inherent to this approach. We critically review previous approaches and discuss designs for clinical trials that seem appropriate to the investigation of conditioned placebo effects in pharmacotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Efficacy of alternate day versus daily dosing of rosuvastatin

PubMed Central

Dulay, Daisy; LaHaye, Stephen A; Lahey, Karen A; Day, Andrew G

2009-01-01

BACKGROUND: Compared with other statins, rosuvastatin has a relatively long half-life, which may allow for the administration of this medication on an alternate day basis. OBJECTIVE: To compare the efficacy of administering rosuvastatin on a daily basis versus on an alternate day basis for the treatment of dyslipidemia. METHODS: In the present crossover study, 45 patients with documented hypercholesterolemia requiring pharmacotherapy were administered either 20 mg of rosuvastatin on alternate days or 10 mg of rosuvastatin daily for six weeks. After a four-week washout period, patients were then switched to the other regimen for another six weeks. The primary end point was the percentage reduction of low-density lipoprotein cholesterol (LDL-C). RESULTS: LDL-C decreased by 48.5% versus 40.9% with daily and alternate day dosing, respectively. This represented an additional absolute reduction of LDL-C of 7.6% (95% CI 1.8% to 13.4%, P=0.012) with the daily dosing regimen. Both dosing regimens provided similar improvements in high-density lipoprotein cholesterol and triglycerides. CONCLUSIONS: Compared with alternate day dosing, daily dosing of rosuvastatin provides a statistically significant advantage in LDL-C reduction. However, the alternate day regimen may be a viable option for those patients in whom cost is a limitation to compliance. PMID:19214297

Editor's choice--Use of disposable radiation-absorbing surgical drapes results in significant dose reduction during EVAR procedures.

PubMed

Kloeze, C; Klompenhouwer, E G; Brands, P J M; van Sambeek, M R H M; Cuypers, P W M; Teijink, J A W

2014-03-01

Because of the increasing number of interventional endovascular procedures with fluoroscopy and the corresponding high annual dose for interventionalists, additional dose-protecting measures are desirable. The purpose of this study was to evaluate the effect of disposable radiation-absorbing surgical drapes in reducing scatter radiation exposure for interventionalists and supporting staff during an endovascular aneurysm repair (EVAR) procedure. This was a randomized control trial in which 36 EVAR procedures were randomized between execution with and without disposable radiation-absorbing surgical drapes (Radpad: Worldwide Innovations & Technologies, Inc., Kansas City, US, type 5511A). Dosimetric measurements were performed on the interventionalist (hand and chest) and theatre nurse (chest) with and without the use of the drapes to obtain the dose reduction and effect on the annual dose caused by the drapes. Use of disposable radiation-absorbing surgical drapes resulted in dose reductions of 49%, 55%, and 48%, respectively, measured on the hand and chest of the interventionalist and the chest of the theatre nurse. The use of disposable radiation-absorbing surgical drapes significantly reduces scatter radiation exposure for both the interventionalist and the supporting staff during EVAR procedures. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Dissociation between the effects of P1, P4-diadenosine tetraphosphate (Ap4A) on renal haemodynamics and tubular function in anaesthetized rats.

PubMed

Jankowski, M; Angielski, S; Szczepańska-Konkel, M

2008-03-01

Previous studies from our laboratory have reported a marked reduction in glomerular filtration rate (GFR) and sodium reabsorption in renal proximal tubule during intravenous infusion of P(1),P(4)-diadenosine tetraphosphate (Ap(4)A) at dose of 1.0 micromol/kg + 10 nmol/kg/min (i.v., injection followed by infusion) in anaesthetized Wistar rats. In the present study, the changes of GFR and urine sodium excretion were investigated in response to systemic infusion of Ap(4)A at different doses. Ap(4)A at dose of 0.1 micromol/kg + 1.0 nmol/kg/min did not change GFR and sodium urinary excretion whereas 2-fold higher dose produced significant (3.4-fold) increase in sodium excretion without changes in GFR. Significant but transient reduction in GFR by approximately 21% was observed during infusion of Ap(4)A at dose of 0.5 micromol/kg + 5.0 nmol/kg/min. Higher doses of Ap(4)A (1.0 micromol/kg + 10 nmol/kg/min and 2.0 micromol/kg + 20 nmol/kg/min) reduction in GFR and marked natriuresis. Our results suggest that tubular sodium transport systems are more sensitive to Ap(4)A than systems involved in GFR regulation.

Hyperhidrosis in association with efavirenz.

PubMed

Fuertes, Aurelio; Martín, Aurelio Fuertes; Cabrera, Salvador; Figueroa, Salvador Cabrera; Valverde, Maria de la Paz; Merino, María de la Paz Valverde; Domínguez-Gil, Alfonso; Hurléé, Alfonso Domínguez-Gil

2009-03-01

Hyperhidrosis may be an adverse drug event (ADE) induced by the effect on any of the components of human thermoregulation. Some of our efavirenz (EFV)-treated patients have reported excessive nocturnal sweating that resolved after dose reduction. A representative clinical case of a male patient being treated with a night-time 600-mg dose of EFV who reported severe nocturnal sweating is reported here. His EFV plasma concentrations were always above normal and he was homozygous for a deficient function-allele of CYP2D6; for this reason, his EFV dose was reduced to 400mg=d. Simultaneous with this reduction, the patient described a progressive decrease in nocturnal sweating until its complete disappearance 15-20 days after this new drug dosage. The mechanism explaining sweating could be similar to the one suggested for hyperhidrosis related to serotonin uptake inhibitors, because this hyperhidrosis is episodic, nocturnal, and dose dependent. Hyperhidrosis could correspond to a dose-dependent ADE induced by EFV, therefore, a reduction of EFV from 600 to 400mg/d seems to control it. EFV crosses the hematoencephalic barrier and reaches a mean concentration in the cerebroespinal fluid equivalent to 0.69% of the plasma concentration. The ability of EFV to accessing the central nervous system (CNS) could explain an effect on thermoregulation. Hyperhydrosis is not easily discovered through a routine anamnesis because it is not noted on the EFV package insert, so its incidence may be higher than expected. Additionally, hyperhidrosis may be an indicator of elevated EFV plasma concentrations and hence may be controlled through a reduction of dose.

Does dose matter in reducing gestational weight gain in exercise interventions? A systematic review of literature.

PubMed

McDonald, Samantha M; Liu, Jihong; Wilcox, Sara; Lau, Erica Y; Archer, Edward

2016-04-01

The purpose of this review was to examine the relationship between exercise dose and reductions in weight gain during pregnancy in exercise interventions. Systematic literature review. Four electronic research databases (PubMed, Web of Science, CINAHL, and Academic Search Premiere) were used to identify exercise interventions conducted with pregnant women. Eligible articles must have satisfied the following criteria: inclusion of a control condition, exercise as a major intervention component, weight gain measured and reported for each experimental condition, description of exercise dose (frequency, intensity and duration), and utilized an adequate number of control conditions to assess independent effects of exercise on weight gain. The literature search identified 4837 articles. Of these, 174 abstracts were screened and 21 intervention studies (18 exercise-only, 3 exercise/diet) were eligible for review. Only 38% of the interventions achieved statistically significant reductions in gestational weight gain. Successful interventions possessed higher adherence and lower attrition rates and were predominantly conducted among normal weight populations. No clear patterns or consistencies of exercise dose and reductions in weight gain were evident. An exercise dose associated with reductions in weight gain was unquantifiable among these interventions. Adherence and retention rates were strong contributors to the success of exercise interventions on gestational weight gain. It is strongly suggested that future researchers investigate methods to increase adherence and compliance, especially among overweight and obese women, and utilize objective measurement tools to accurately evaluate exercise dose performed by the participants and the impact on body composition and weight gain. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Evaluation of patritumab with or without erlotinib in combination with standard cytotoxic agents against pediatric sarcoma xenograft models.

PubMed

Bandyopadhyay, Abhik; Favours, Edward; Phelps, Doris A; Pozo, Vanessa Del; Ghilu, Samson; Kurmashev, Dias; Michalek, Joel; Trevino, Aron; Guttridge, Denis; London, Cheryl; Hirotani, Kenji; Zhang, Ling; Kurmasheva, Raushan T; Houghton, Peter J

2018-02-01

Integrating molecularly targeted agents with cytotoxic drugs used in curative treatment of pediatric cancers is complex. An evaluation was undertaken with the ERBB3/Her3-specific antibody patritumab (P) either alone or with the ERBB1/epidermal growth factor receptor inhibitor erlotinib (E) in combination with standard cytotoxic agents, cisplatin, vincristine, and cyclophosphamide, in pediatric sarcoma xenograft models that express receptors and ligands targeted by these agents. Tumor models were selected based upon ERBB3 expression and phosphorylation, and ligand (heregulin) expression. Patritumab, E, or these agents combined was evaluated without or with concomitant cytotoxic agents using procedures developed by the Pediatric Preclinical Testing Program. Full doses of cytotoxic agents were tolerated when combined with P, whereas dose reductions of 25% (vincristine, cisplatin) or 50% (cyclophosphamide) were required when combined with P + E. Patritumab, E alone, or in combination did not significantly inhibit growth of any tumor model, except for Rh18 xenografts (E alone). Patritumab had no single-agent activity and marginally enhanced the activity of vincristine and cisplatin only in Ewing sarcoma ES-4. P + E did not increase the antitumor activity of vincristine or cisplatin, whereas dose-reduced cyclophosphamide was significantly less active than cyclophosphamide administered at its maximum tolerated dose when combined with P + E. P had no single-agent activity, although it marginally potentiated the activity of vincristine and cisplatin in one of three models studied. However, the addition of E necessitated dose reduction of each cytotoxic agent, abrogating the enhancement observed with P alone. © 2017 Wiley Periodicals, Inc.

Emerging Techniques for Dose Optimization in Abdominal CT

PubMed Central

Platt, Joel F.; Goodsitt, Mitchell M.; Al-Hawary, Mahmoud M.; Maturen, Katherine E.; Wasnik, Ashish P.; Pandya, Amit

2014-01-01

Recent advances in computed tomographic (CT) scanning technique such as automated tube current modulation (ATCM), optimized x-ray tube voltage, and better use of iterative image reconstruction have allowed maintenance of good CT image quality with reduced radiation dose. ATCM varies the tube current during scanning to account for differences in patient attenuation, ensuring a more homogeneous image quality, although selection of the appropriate image quality parameter is essential for achieving optimal dose reduction. Reducing the x-ray tube voltage is best suited for evaluating iodinated structures, since the effective energy of the x-ray beam will be closer to the k-edge of iodine, resulting in a higher attenuation for the iodine. The optimal kilovoltage for a CT study should be chosen on the basis of imaging task and patient habitus. The aim of iterative image reconstruction is to identify factors that contribute to noise on CT images with use of statistical models of noise (statistical iterative reconstruction) and selective removal of noise to improve image quality. The degree of noise suppression achieved with statistical iterative reconstruction can be customized to minimize the effect of altered image quality on CT images. Unlike with statistical iterative reconstruction, model-based iterative reconstruction algorithms model both the statistical noise and the physical acquisition process, allowing CT to be performed with further reduction in radiation dose without an increase in image noise or loss of spatial resolution. Understanding these recently developed scanning techniques is essential for optimization of imaging protocols designed to achieve the desired image quality with a reduced dose. © RSNA, 2014 PMID:24428277

Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

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

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation daymore » (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.« less

Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

PubMed

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.

Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

PubMed

Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

2011-03-01

The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

MLC-based penumbra softener of EDW borders to reduce junction inhomogeneities.

PubMed

Szpala, Stanislaw; Kohli, Kirpal

2017-05-01

Junctions of fields are known to be susceptible to developing cold or hot spots in the presence of even small geometrical misalignments. Reduction of these dose inhomogeneities can be accomplished through decreasing the dose gradients in the penumbra, but currently it cannot be done for enhanced dynamic wedges (EDW). An MLC-based penumbra softener was developed in the developer mode of TrueBeam linacs to reduce dose gradients across the side border of EDWs. The movement of each leaf was individually synchronized with the movement of the dynamic Y jaw to soften the penumbra in the same manner along the entire field border, in spite of the presence of the dose gradient of the EDW. Junction homogeneity upon field misalignment for side-matched EDWs was examined with the MV imager. The fluence inhomogeneities were reduced from about 30% per mm of shift of the field borders for the conventional EDW to about 2% per mm for the softened-penumbra plan. The junction in a four-field monoisocentric breast plan delivered to the Rando phantom was assessed with film. The dose inhomogeneities across the junction in the superior-inferior direction were reduced from about 20% to 25% per mm for the conventional fields to about 5% per mm. The dose near the softened junction of the breast plan with no shifts did not deviate from the conventional plan by more than about 4%. The newly-developed softened-penumbra junction of EDW (and/or open) fields was shown to reduce sensitivity to misalignments without increasing complexity of the planning or delivery. This methodology needs to be adopted by the manufacturers for clinical use. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A Daily Dose of CALM: Supporting Middle School Educators' Wellbeing and Classroom Functioning through a Brief Stress Reduction Intervention

ERIC Educational Resources Information Center

Harris, Alexis R.; Jennings, Patricia A.; Abenavoli, Rachel M.; Katz, Deirdre A.; Greenberg, Mark T.; Schussler, Deborah

2014-01-01

The current study involved the development, implementation, and evaluation of a universal school-based intervention designed to promote health and wellbeing among educators. This study aims to further investigate the efficacy of contemplative practices as a support for teacher wellbeing. The study contributes a new perspective to the current…

Dose addition predicts the effects of a mixture of five phthalate esters to inhibit fetal testosterone production and gene expression, and postnatal reproductive development in the Sprague Dawley rat

EPA Science Inventory

Exposure to some phthalate esters (PE) during sexual differentiation induces reproductive malformations in male and female rats. In the fetal male, these lesions result from phthalate-induced reductions in testicular testosterone (T) production and insulin-like hormone 3 (insl3) ...

Varicella prevention in Costa Rica: impact of a one-dose schedule universal vaccination.

PubMed

Avila-Aguero, María L; Ulloa-Gutierrez, Rolando; Camacho-Badilla, Kattia; Soriano-Fallas, Alejandra; Arroba-Tijerino, Roberto; Morice-Trejos, Ana

2017-03-01

To describe the impact following a 1-dose Varicella vaccination schedule introduced in Costa Rica in September 2007. Areas covered: This is a retrospective review using epidemiologic surveillance national databases of varicella cases and hospitalizations, period 2000-2015. We analyzed age-related varicella incidence cases and hospitalization trends before and after the vaccine introduction. Expert commentary: Varicella vaccine coverage among children 16 months age increased from 76% in 2008 to 95% in 2015. During this period Costa Rica reached a 73.8% reduction of Varicella reported cases and 85.9% reduction of hospitalizations in the general population. Among children under 5 years of age, that reduction was 79.1% and 87%, respectively. Varicella complications in hospitalized patients decreased 98%, from n = 53 in 2008 to n = 1 in 2014. After 8-years post implementation of a 1-dose schedule of universal varicella vaccination, a dramatic overall disease reduction in incidence, hospitalizations and complicated cases has been observed in all age groups.

Impact of high-dose atorvastatin therapy and clinical risk factors on incident aortic valve stenosis in patients with cardiovascular disease (from TNT, IDEAL, and SPARCL).

PubMed

Arsenault, Benoit J; Boekholdt, S Matthijs; Mora, Samia; DeMicco, David A; Bao, Weihang; Tardif, Jean-Claude; Amarenco, Pierre; Pedersen, Terje; Barter, Philip; Waters, David D

2014-04-15

Clinical trials have not provided evidence for a role of statin therapy in reducing aortic valve stenosis (AVS) severity in patients with documented AVS. However, whether statin therapy could prevent the onset of AVS is unknown. Our objectives were (1) to compare the incidence rates of AVS among patients treated with high-dose versus usual-dose statin or placebo and (2) to identify clinical risk factors associated with the development of AVS. We conducted post hoc analyses in 23,508 participants from 3 large-scale multicenter atorvastatin randomized blinded clinical trials: Treating to New Targets, the Incremental Decrease in End Points Through Aggressive Lipid Lowering, and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels. The main outcome measure was the incidence of clinical AVS over a median follow-up of 4.9 years (82 cases). Among patients who developed AVS, 39 (47.6%) were treated with atorvastatin 80 mg and 43 (52.4%) were treated with lower dose statin (atorvastatin 10 mg in Treating to New Targets, simvastatin 20 to 40 mg in Incremental Decrease in End Points Through Aggressive Lipid Lowering, or placebo in Stroke Prevention by Aggressive Reduction in Cholesterol Levels; hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.59 to 1.41, p=0.67). In multivariate analyses forcing treatment, sex, and race into the model, factors that were significantly associated with AVS included age (HR 2.17, 95% CI 1.61 to 2.93, p<0.0001 per 1-SD increment), diabetes (HR 1.67, 95% CI 1.00 to 2.80, p=0.05), vitamin K antagonist use (HR 3.25, 95% CI 2.06 to 5.16, p<0.0001), and previous statin use (HR 2.65, 95% CI 1.54 to 4.60, p=0.0008). In conclusion, random allocation to high-dose versus usual-dose statin therapy or placebo did not impact the incidence of AVS among patients without known AVS. Age, diabetes, vitamin K antagonists, and previous statin use were significant predictors of incident AVS in these high-risk patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Technique for comprehensive head and neck irradiation using 3-dimensional conformal proton therapy

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

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, IN; Walter, Alexander S.

2015-01-01

Owing to the technical and logistical complexities of matching photon and proton treatment modalities, we developed and implemented a technique of comprehensive head and neck radiation using 3-dimensional (3D) conformal proton therapy. A monoisocentric technique was used with a 30-cm snout. Cervical lymphatics were treated with 3 fields: a posterior-anterior field with a midline block and a right and a left posterior oblique field. The matchline of the 3 cervical nodal fields with the primary tumor site fields was staggered by 0.5 cm. Comparative intensity-modulated photon plans were later developed for 12 previously treated patients to provide equivalent target coverage,more » while matching or improving on the proton plans' sparing of organs at risk (OARs). Dosimetry to OARs was evaluated and compared by treatment modality. Comprehensive head and neck irradiation using proton therapy yielded treatment plans with significant dose avoidance of the oral cavity and midline neck structures. When compared with the generated intensity-modulated radiation therapy (IMRT) plans, the proton treatment plans yielded statistically significant reductions in the mean and integral radiation dose to the oral cavity, larynx, esophagus, and the maximally spared parotid gland. There was no significant difference in mean dose to the lesser-spared parotid gland by treatment modality or in mean or integral dose to the spared submandibular glands. A technique for cervical nodal irradiation using 3D conformal proton therapy with uniform scanning was developed and clinically implemented. Use of proton therapy for cervical nodal irradiation resulted in large volume of dose avoidance to the oral cavity and low dose exposure to midline structures of the larynx and the esophagus, with lower mean and integral dose to assessed OARs when compared with competing IMRT plans.« less

SU-C-18C-06: Radiation Dose Reduction in Body Interventional Radiology: Clinical Results Utilizing a New Imaging Acquisition and Processing Platform

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

Kohlbrenner, R; Kolli, KP; Taylor, A

2014-06-01

Purpose: To quantify the patient radiation dose reduction achieved during transarterial chemoembolization (TACE) procedures performed in a body interventional radiology suite equipped with the Philips Allura Clarity imaging acquisition and processing platform, compared to TACE procedures performed in the same suite equipped with the Philips Allura Xper platform. Methods: Total fluoroscopy time, cumulative dose area product, and cumulative air kerma were recorded for the first 25 TACE procedures performed to treat hepatocellular carcinoma (HCC) in a Philips body interventional radiology suite equipped with Philips Allura Clarity. The same data were collected for the prior 85 TACE procedures performed to treatmore » HCC in the same suite equipped with Philips Allura Xper. Mean values from these cohorts were compared using two-tailed t tests. Results: Following installation of the Philips Allura Clarity platform, a 42.8% reduction in mean cumulative dose area product (3033.2 versus 1733.6 mGycm∧2, p < 0.0001) and a 31.2% reduction in mean cumulative air kerma (1445.4 versus 994.2 mGy, p < 0.001) was achieved compared to similar procedures performed in the same suite equipped with the Philips Allura Xper platform. Mean total fluoroscopy time was not significantly different between the two cohorts (1679.3 versus 1791.3 seconds, p = 0.41). Conclusion: This study demonstrates a significant patient radiation dose reduction during TACE procedures performed to treat HCC after a body interventional radiology suite was converted to the Philips Allura Clarity platform from the Philips Allura Xper platform. Future work will focus on evaluation of patient dose reduction in a larger cohort of patients across a broader range of procedures and in specific populations, including obese patients and pediatric patients, and comparison of image quality between the two platforms. Funding for this study was provided by Philips Healthcare, with 5% salary support provided to authors K. Pallav Kolli and Robert G. Gould for time devoted to the study. Data acquisition and analysis was performed by the authors independent of the funding source.« less

Conebeam CT of the head and neck, part 1: physical principles.

PubMed

Miracle, A C; Mukherji, S K

2009-06-01

Conebeam x-ray CT (CBCT) is a developing imaging technique designed to provide relatively low-dose high-spatial-resolution visualization of high-contrast structures in the head and neck and other anatomic areas. This first installment in a 2-part review will address the physical principles underlying CBCT imaging as it is used in dedicated head and neck scanners. Concepts related to CBCT acquisition geometry, flat panel detection, and image quality will be explored in detail. Particular emphasis will be placed on technical limitations to low-contrast detectability and radiation dose. Proposed methods of x-ray scatter reduction will also be discussed.

The impact of smart metal artefact reduction algorithm for use in radiotherapy treatment planning.

PubMed

Guilfoile, Connor; Rampant, Peter; House, Michael

2017-06-01

The presence of metal artefacts in computed tomography (CT) create issues in radiation oncology. The loss of anatomical information and incorrect Hounsfield unit (HU) values produce inaccuracies in dose calculations, providing suboptimal patient treatment. Metal artefact reduction (MAR) algorithms were developed to combat these problems. This study provides a qualitative and quantitative analysis of the "Smart MAR" software (General Electric Healthcare, Chicago, IL, USA), determining its usefulness in a clinical setting. A detailed analysis was conducted using both patient and phantom data, noting any improvements in HU values and dosimetry with the GE-MAR enabled. This study indicates qualitative improvements in severity of the streak artefacts produced by metals, allowing for easier patient contouring. Furthermore, the GE-MAR managed to recover previously lost anatomical information. Additionally, phantom data showed an improvement in HU value with GE-MAR correction, producing more accurate point dose calculations in the treatment planning system. Overall, the GE-MAR is a useful tool and is suitable for clinical environments.

In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice.

PubMed

Fentahun, Selamawit; Makonnen, Eyasu; Awas, Tesfaye; Giday, Mirutse

2017-01-05

Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.

[Fluoroscopy dose reduction of computed tomography guided chest interventional radiology using real-time iterative reconstruction].

PubMed

Hasegawa, Hiroaki; Mihara, Yoshiyuki; Ino, Kenji; Sato, Jiro

2014-11-01

The purpose of this study was to evaluate the radiation dose reduction to patients and radiologists in computed tomography (CT) guided examinations for the thoracic region using CT fluoroscopy. Image quality evaluation of the real-time filtered back-projection (RT-FBP) images and the real-time adaptive iterative dose reduction (RT-AIDR) images was carried out on noise and artifacts that were considered to affect the CT fluoroscopy. The image standard deviation was improved in the fluoroscopy setting with less than 30 mA on 120 kV. With regard to the evaluation of artifact visibility and the amount generated by the needle attached to the chest phantom, there was no significant difference between the RT-FBP images with 120 kV, 20 mA and the RT-AIDR images with low-dose conditions (greater than 80 kV, 30 mA and less than 120 kV, 20 mA). The results suggest that it is possible to reduce the radiation dose by approximately 34% at the maximum using RT-AIDR while maintaining image quality equivalent to the RT-FBP images with 120 V, 20 mA.

Urethra sparing - potential of combined Nickel-Titanium stent and intensity modulated radiation therapy in prostate cancer.

PubMed

Thomsen, Jakob Borup; Arp, Dennis Tideman; Carl, Jesper

2012-05-01

To investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model. This theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel-Titanium (Ni-Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose. The feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability. A new concept for urethra dose reduction is presented. The method relies on the use of a Ni-Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Kilovoltage Imaging Doses in the Radiotherapy of Pediatric Cancer Patients

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

Deng Jun, E-mail: jun.deng@yale.edu; Chen Zhe; Roberts, Kenneth B.

Purpose: To investigate doses induced by kilovoltage cone-beam computed tomography (kVCBCT) to pediatric cancer patients undergoing radiotherapy, as well as strategies for dose reduction. Methods and Materials: An EGS4 Monte Carlo code was used to calculate three-dimensional dose deposition due to kVCBCT on 4 pediatric cancer patients. Absorbed doses to various organs were analyzed for both half-fan and full-fan modes. Clinical conditions, such as distance from organ at risk (OAR) to CBCT field border, kV peak energy, and testicular shielding, were studied. Results: The mean doses induced by one CBCT scan operated at 125 kV in half-fan mode to testes,more » liver, kidneys, femoral heads, spinal cord, brain, eyes, lens, and optical nerves were 2.9, 4.7, 7.7, 10.5, 8.8, 7.6, 7.7, 7.8, and 7.2 cGy, respectively. Increasing the distances from OARs to CBCT field border greatly reduced the doses to OARs, ranging from 33% reduction for spinal cord to 2300% reduction for testes. As photon beam energy increased from 60 to 125 kV, the dose increase due to kVCBCT ranged from 170% for lens to 460% for brain and spinal cord. A testicular shielding made of 1-cm cerrobend could reduce CBCT doses down to 31%, 51%, 68%, and 82%, respectively, for 60, 80, 100, and 125 kV when the testes lay within the CBCT field. Conclusions: Generally speaking, kVCBCT deposits much larger doses to critical structures in children than in adults, usually by a factor of 2 to 3. Increasing the distances from OARs to CBCT field border greatly reduces doses to OARs. Depending on OARs, kVCBCT-induced doses increase linearly or exponentially with photon beam energy. Testicular shielding works more efficiently at lower kV energies. On the basis of our study, it is essential to choose an appropriate scanning protocol when kVCBCT is applied to pediatric cancer patients routinely.« less

A Third-Generation Adaptive Statistical Iterative Reconstruction Technique: Phantom Study of Image Noise, Spatial Resolution, Lesion Detectability, and Dose Reduction Potential.

PubMed

Euler, André; Solomon, Justin; Marin, Daniele; Nelson, Rendon C; Samei, Ehsan

2018-06-01

The purpose of this study was to assess image noise, spatial resolution, lesion detectability, and the dose reduction potential of a proprietary third-generation adaptive statistical iterative reconstruction (ASIR-V) technique. A phantom representing five different body sizes (12-37 cm) and a contrast-detail phantom containing lesions of five low-contrast levels (5-20 HU) and three sizes (2-6 mm) were deployed. Both phantoms were scanned on a 256-MDCT scanner at six different radiation doses (1.25-10 mGy). Images were reconstructed with filtered back projection (FBP), ASIR-V with 50% blending with FBP (ASIR-V 50%), and ASIR-V without blending (ASIR-V 100%). In the first phantom, noise properties were assessed by noise power spectrum analysis. Spatial resolution properties were measured by use of task transfer functions for objects of different contrasts. Noise magnitude, noise texture, and resolution were compared between the three groups. In the second phantom, low-contrast detectability was assessed by nine human readers independently for each condition. The dose reduction potential of ASIR-V was estimated on the basis of a generalized linear statistical regression model. On average, image noise was reduced 37.3% with ASIR-V 50% and 71.5% with ASIR-V 100% compared with FBP. ASIR-V shifted the noise power spectrum toward lower frequencies compared with FBP. The spatial resolution of ASIR-V was equivalent or slightly superior to that of FBP, except for the low-contrast object, which had lower resolution. Lesion detection significantly increased with both ASIR-V levels (p = 0.001), with an estimated radiation dose reduction potential of 15% ± 5% (SD) for ASIR-V 50% and 31% ± 9% for ASIR-V 100%. ASIR-V reduced image noise and improved lesion detection compared with FBP and had potential for radiation dose reduction while preserving low-contrast detectability.

Pulsed electromagnetic fields dosing impacts postoperative pain in breast reduction patients.

PubMed

Taylor, Erin M; Hardy, Krista L; Alonso, Amanda; Pilla, Arthur A; Rohde, Christine H

2015-01-01

Pulsed electromagnetic fields (PEMF) reduce postoperative pain and narcotic requirements in breast augmentation, reduction, and reconstruction patients. PEMF enhances both calmodulin-dependent nitric oxide and/or cyclic guanosine monophosphate signaling and phosphodiesterase activity, which blocks cyclic guanosine monophosphate. The clinical effect of these competing responses on PEMF dosing is not known. Two prospective, nonrandomized, active cohorts of breast reduction patients, with 15 min PEMF per 2 h; "Q2 (active)", and 5 min PEMF per 20 min; "5/20 (active)", dosing regimens were added to a previously reported double-blind clinical study wherein 20 min PEMF per 4 h, "Q4 (active)", dosing significantly accelerated postoperative pain reduction compared with Q4 shams. Postoperative visual analog scale pain scores and narcotic use were compared with results from the previous study. Visual analog scale scores at 24 h were 43% and 35% of pain at 1 h in the Q4 (active) and Q2 (active) cohorts, respectively (P < 0.01). Pain at 24 h in the 5/20 (active) cohort was 87% of pain at 1 h, compared with 74% in the Q4 (sham) cohort (P = 0.451). Concomitantly, narcotic usage in the 5/20 (active) and Q4 (sham) cohorts was not different (P = 0.478), and 2-fold higher than the Q4 (active) and Q2 (active) cohorts (P < 0.02). This prospective study shows Q4/Q2, but not 5/20 PEMF dosing, accelerated postoperative pain reduction compared with historical shams. The 5/20 (active) regimen increases NO 4-fold faster than the Q4 (active) regimen, possibly accelerating phosphodiesterase inhibition of cyclic guanosine monophosphate sufficiently to block the PEMF effect. This study helps define the dosing limits of clinically useful PEMF signals. Copyright © 2015 Elsevier Inc. All rights reserved.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Recent Developments in Computed Tomography for Urolithiasis: Diagnosis and Characterization

PubMed Central

Mc Laughlin, P. D.; Crush, L.; Maher, M. M.; O'Connor, O. J.

2012-01-01

Objective. To critically evaluate the current literature in an effort to establish the current role of radiologic imaging, advances in computed tomography (CT) and standard film radiography in the diagnosis, and characterization of urinary tract calculi. Conclusion. CT has a valuable role when utilized prudently during surveillance of patients following endourological therapy. In this paper, we outline the basic principles relating to the effects of exposure to ionizing radiation as a result of CT scanning. We discuss the current developments in low-dose CT technology, which have resulted in significant reductions in CT radiation doses (to approximately one-third of what they were a decade ago) while preserving image quality. Finally, we will discuss an important recent development now commercially available on the latest generation of CT scanners, namely, dual energy imaging, which is showing promise in urinary tract imaging as a means of characterizing the composition of urinary tract calculi. PMID:22952473

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy.

PubMed

Depositario-Cabacar, Dewi T; Peters, Jurriaan M; Pong, Amanda W; Roth, Julie; Rotenberg, Alexander; Riviello, James J; Takeoka, Masanori

2010-07-01

We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

Comparing Pain and Depressive Symptoms of Chronic Opioid Therapy Patients Receiving Dose Reduction and Risk Mitigation Initiatives With Usual Care.

PubMed

Thakral, Manu; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha; Von Korff, Michael

2018-01-01

Dose reduction and risk mitigation initiatives have been recommended to reduce opioid-related risks among patients receiving chronic opioid therapy (COT), but questions remain over whether these initiatives worsen pain control and quality of life. In 2014 to 2015, we interviewed 1,588 adult COT patients within a health care system in Washington State and compared those who received dose reduction and risk mitigation initiatives in primary care clinics (intervention) with patients in comparable health care settings without initiatives (control). The primary outcomes were pain assessed using the pain, enjoyment, and general activity (PEG) scale, a 3-item scale to assess global pain intensity and interference, with secondary measures including depression (Patient Health Questionnaire-8 scale). Generalized estimating equations for linear regression models were used to estimate differences in mean scores between intervention and control sites. Estimated differences, adjusted for patient characteristics and weighted for nonresponse, between patients at intervention and control clinics were not clinically significant for the PEG (-.03, 95% confidence interval = -.25 to .19) or Patient Health Questionnaire-8 (-.64, 95% confidence interval = -1.19 to -.08). We found no evidence that COT patients in clinics with dose reduction and risk mitigation initiatives had clinically meaningful differences in pain intensity, interference with activities and enjoyment of life, or depressive symptoms compared with control health care settings. This article evaluates the effect of dose reduction and risk mitigation initiatives, such as those recently recommended by the Centers for Disease Control and Prevention, to reduce risks associated with COT on global pain and interference, depressive symptoms, and perceived pain relief and bothersomeness of side effects. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study.

PubMed

Sgouros, Joseph; Aravantinos, Gerasimos; Kouvatseas, George; Rapti, Anna; Stamoulis, George; Bisvikis, Anastasios; Res, Helen; Samantas, Epameinondas

2015-12-01

Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy.

PubMed

Sharfo, Abdul Wahab M; Breedveld, Sebastiaan; Voet, Peter W J; Heijkoop, Sabrina T; Mens, Jan-Willem M; Hoogeman, Mischa S; Heijmen, Ben J M

2016-01-01

To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible.

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

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

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

Preliminary validation of a new methodology for estimating dose reduction protocols in neonatal chest computed radiographs

NASA Astrophysics Data System (ADS)

Don, Steven; Whiting, Bruce R.; Hildebolt, Charles F.; Sehnert, W. James; Ellinwood, Jacquelyn S.; Töpfer, Karin; Masoumzadeh, Parinaz; Kraus, Richard A.; Kronemer, Keith A.; Herman, Thomas; McAlister, William H.

2006-03-01

The risk of radiation exposure is greatest for pediatric patients and, thus, there is a great incentive to reduce the radiation dose used in diagnostic procedures for children to "as low as reasonably achievable" (ALARA). Testing of low-dose protocols presents a dilemma, as it is unethical to repeatedly expose patients to ionizing radiation in order to determine optimum protocols. To overcome this problem, we have developed a computed-radiography (CR) dose-reduction simulation tool that takes existing images and adds synthetic noise to create realistic images that correspond to images generated with lower doses. The objective of our study was to determine the extent to which simulated, low-dose images corresponded with original (non-simulated) low-dose images. To make this determination, we created pneumothoraces of known volumes in five neonate cadavers and obtained images of the neonates at 10 mR, 1 mR and 0.1 mR (as measured at the cassette plate). The 10-mR exposures were considered "relatively-noise-free" images. We used these 10 mR-images and our simulation tool to create simulated 0.1- and 1-mR images. For the simulated and original images, we identified regions of interest (ROI) of the entire chest, free-in-air region, and liver. We compared the means and standard deviations of the ROI grey-scale values of the simulated and original images with paired t tests. We also had observers rate simulated and original images for image quality and for the presence or absence of pneumothoraces. There was no statistically significant difference in grey-scale-value means nor standard deviations between simulated and original entire chest ROI regions. The observer performance suggests that an exposure >=0.2 mR is required to detect the presence or absence of pneumothoraces. These preliminary results indicate that the use of the simulation tool is promising for achieving ALARA exposures in children.

Gonad dose in AP pelvis radiography: Impact of anode heel orientation.

PubMed

Mraity, H A A B; England, A; Hogg, P

2017-02-01

For antero posterior (AP) pelvis radiographic examination, determine the impact of anode heel orientation on female/male gonad dose. High sensitivity thermo-luminescent dosimeters (TLDs) were used with an ATOM dosimetry phantom; the phantom was positioned for AP pelvis. TLDs were placed into the testes and ovaries. Radiation dose received by these organs was measured with the feet toward anode and feet toward the cathode. kVp, mAs and SID were manipulated to generate a range of exposures. A dose profile was also generated using Unfors Mult-O-Meter 401 along the long axis of the phantom. A decrease in dose from the central ray toward the anode was noted, with a marked increase toward the cathode. A significant reduction in dose was received by the testes with feet towards the anode compared with feet towards cathode (P˂0.001). No difference was seen for ovarian dose (P˃0.05). kVp, mAs and SID all have an effect on male and female gonad dose. For male pelvis imaging, placing feet towards the anode can be used as a simple dose reduction method. Copyright © 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

PubMed Central

Hawwa, Ahmed F; Collier, Paul S; Millership, Jeff S; McCarthy, Anthony; Dempsey, Sid; Cairns, Carole; McElnay, James C

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself.Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDSThe first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed.The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates.The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype. PMID:18823306

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

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

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less

Reduction factors for wooden houses due to external γ-radiation based on in situ measurements after the Fukushima nuclear accident.

PubMed

Yoshida-Ohuchi, Hiroko; Hosoda, Masahiro; Kanagami, Takashi; Uegaki, Masaki; Tashima, Hideo

2014-12-18

For estimation of residents' exposure dose after a nuclear accident, the reduction factor, which is the ratio of the indoor dose to the outdoor dose is essential, as most individuals spend a large portion of their time indoors. After the Fukushima nuclear accident, we evaluated the median reduction factor with an interquartile range of 0.43 (0.34-0.53) based on 522 survey results for 69 detached wooden houses in two evacuation zones, Iitate village and Odaka district. The results indicated no statistically significant difference in the median reduction factor to the representative value of 0.4 given in the International Atomic Energy Agency (IAEA)-TECDOC-225 and 1162. However, with regard to the representative range of the reduction factor, we recommend the wider range of 0.2 to 0.7 or at least 0.2 to 0.6, which covered 87.7% and 80.7% of the data, respectively, rather than 0.2 to 0.5 given in the IAEA document, which covered only 66.5% of the data. We found that the location of the room within the house and area topography, and the use of cement roof tiles had the greatest influence on the reduction factor.

Sci-Thur PM – Brachytherapy 05: Surface Collimation Applied to Superficial Flap High Dose-Rate Brachytherapy

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

Liu, Derek; Sabondjian, Eric; Lawrence, Kailin

Purpose: To apply surface collimation for superficial flap HDR skin brachytherapy utilizing common clinical resources and to demonstrate the potential for OAR dose reduction within a clinically relevant setting. Methods: Two phantom setups were used. 3 mm lead collimation was applied to a solid slab phantom to determine appropriate geometries relating to collimation and dwell activation. The same collimation was applied to the temple of an anthropomorphic head phantom to demonstrate lens dose reduction. Each setup was simulated and planned to deliver 400 cGy to a 3 cm circular target to 3 mm depth. The control and collimated irradiations weremore » sequentially measured using calibrated radiochromic films. Results: Collimation for the slab phantom attenuated the dose beyond the collimator opening, decreasing the fall-off distances by half and reducing the area of healthy skin irradiated. Target coverage can be negatively impacted by a tight collimation margin, with the required margin approximated by the primary beam geometric penumbra. Surface collimation applied to the head phantom similarly attenuated the surrounding normal tissue dose while reducing the lens dose from 84 to 68 cGy. To ensure consistent setup between simulation and treatment, additional QA was performed including collimator markup, accounting for collimator placement uncertainties, standoff distance verification, and in vivo dosimetry. Conclusions: Surface collimation was shown to reduce normal tissue dose without compromising target coverage. Lens dose reduction was demonstrated on an anthropomorphic phantom within a clinical setting. Additional QA is proposed to ensure treatment fidelity.« less

Radiation dose and image quality in pediatric chest CT: effects of iterative reconstruction in normal weight and overweight children.

PubMed

Yoon, Haesung; Kim, Myung-Joon; Yoon, Choon-Sik; Choi, Jiin; Shin, Hyun Joo; Kim, Hyun Gi; Lee, Mi-Jung

2015-03-01

New CT reconstruction techniques may help reduce the burden of ionizing radiation. To quantify radiation dose reduction when performing pediatric chest CT using a low-dose protocol and 50% adaptive statistical iterative reconstruction (ASIR) compared with age/gender-matched chest CT using a conventional dose protocol and reconstructed with filtered back projection (control group) and to determine its effect on image quality in normal weight and overweight children. We retrospectively reviewed 40 pediatric chest CT (M:F = 21:19; range: 0.1-17 years) in both groups. Radiation dose was compared between the two groups using paired Student's t-test. Image quality including noise, sharpness, artifacts and diagnostic acceptability was subjectively assessed by three pediatric radiologists using a four-point scale (superior, average, suboptimal, unacceptable). Eight children in the ASIR group and seven in the control group were overweight. All radiation dose parameters were significantly lower in the ASIR group (P < 0.01) with a greater than 57% dose reduction in overweight children. Image noise was higher in the ASIR group in both normal weight and overweight children. Only one scan in the ASIR group (1/40, 2.5%) was rated as diagnostically suboptimal and there was no unacceptable study. In both normal weight and overweight children, the ASIR technique is associated with a greater than 57% mean dose reduction, without significantly impacting diagnostic image quality in pediatric chest CT examinations. However, CT scans in overweight children may have a greater noise level, even when using the ASIR technique.

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood

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

Lollert, André, E-mail: andre.lollert@unimedizin-mainz.de; Gies, Christina; Laudemann, Katharina

Purpose: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Methods and Materials: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations throughmore » 2014 (median follow-up time: 48 months). Results: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Conclusions: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy.« less

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood.

PubMed

Lollert, André; Gies, Christina; Laudemann, Katharina; Faber, Jörg; Jacob-Heutmann, Dorothee; König, Jochem; Düber, Christoph; Staatz, Gundula

2016-01-01

The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations through 2014 (median follow-up time: 48 months). A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy. Copyright © 2016. Published by Elsevier Inc.

Radiation dose and image quality of X-ray volume imaging systems: cone-beam computed tomography, digital subtraction angiography and digital fluoroscopy.

PubMed

Paul, Jijo; Jacobi, Volkmar; Farhang, Mohammad; Bazrafshan, Babak; Vogl, Thomas J; Mbalisike, Emmanuel C

2013-06-01

Radiation dose and image quality estimation of three X-ray volume imaging (XVI) systems. A total of 126 patients were examined using three XVI systems (groups 1-3) and their data were retrospectively analysed from 2007 to 2012. Each group consisted of 42 patients and each patient was examined using cone-beam computed tomography (CBCT), digital subtraction angiography (DSA) and digital fluoroscopy (DF). Dose parameters such as dose-area product (DAP), skin entry dose (SED) and image quality parameters such as Hounsfield unit (HU), noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were estimated and compared using appropriate statistical tests. Mean DAP and SED were lower in recent XVI than its previous counterparts in CBCT, DSA and DF. HU of all measured locations was non-significant between the groups except the hepatic artery. Noise showed significant difference among groups (P < 0.05). Regarding CNR and SNR, the recent XVI showed a higher and significant difference compared to its previous versions. Qualitatively, CBCT showed significance between versions unlike the DSA and DF which showed non-significance. A reduction of radiation dose was obtained for the recent-generation XVI system in CBCT, DSA and DF. Image noise was significantly lower; SNR and CNR were higher than in previous versions. The technological advancements and the reduction in the number of frames led to a significant dose reduction and improved image quality with the recent-generation XVI system. • X-ray volume imaging (XVI) systems are increasingly used for interventional radiological procedures. • More modern XVI systems use lower radiation doses compared with earlier counterparts. • Furthermore more modern XVI systems provide higher image quality. • Technological advances reduce radiation dose and improve image quality.

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

PubMed Central

Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

2016-01-01

Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

PubMed

Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

2012-01-01

Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

Development and evaluation of a multidisciplinary controlled substances committee within a patient-centered medical home.

PubMed

Gernant, Stephanie A; Bastien, Rachel; Lai, Andrea

2015-01-01

To present the development of a multidisciplinary controlled substances committee and describe its effectiveness in relation to prescribers' acceptance of committee recommendations, the number of premature deaths associated with controlled substances, and prescribers' need for education on controlled substances. A patient-centered medical home and accountable care organization in Maine that serves more than 60,000 patients across a large rural area, 70% of whom are classified as lower income. A multidisciplinary group of prescribers and PharmD residents created a committee to influence organizational culture regarding controlled substances. The Controlled Substances Initiative Committee (CSIC) updated institutional policies, developed provider education, and made personalized patient recommendations to prescribers. The primary outcome was average change in daily morphine equivalent dose (MED) in patients for whom CSIC recommended a dose reduction to the patient's prescriber. Secondary outcomes included the proportion of patients who died of a known overdose or suspected drug-related death during 2012-2013 or 2013-2014. In addition, prescriber beliefs about controlled substances were measured via a needs assessment. The average daily MED for patients whom CSIC recommended dose reduction was lower after 3 months compared with at baseline (175.5 ± 344.3 mg vs. 292.7 ± 466.5 mg; P <0.05). The proportion of patients who died of a known overdose did not differ between 2012-2013 and 2013-2014 (11.8% vs. 11.1%; P = 1.00). However, a greater number of patients had a suspected drug-related death during 2013-2014 compared with during 2012-2013 (0% vs. 27.3%; P = 0.05). A multidisciplinary controlled substances committee may improve patient safety and outcomes by offering prescriber support and helping alter prescribing culture.

Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims.

PubMed

Lin, Fang-Ju; Lin, Hung-Wei; Ho, Yunn-Fang

2018-04-01

Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013). Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness. Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized. The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.

Efficacy of Lens Protection Systems: Dependency on Different Cranial CT Scans in The Acute Stroke Setting.

PubMed

Guberina, Nika; Forsting, Michael; Ringelstein, Adrian

2017-06-15

To evaluate the dose-reduction potential with different lens protectors for patients undergoing cranial computed tomography (CT) scans. Eye lens dose was assessed in vitro (α-Al2O3:C thermoluminescence dosemeters) using an Alderson-Rando phantom® in cranial CT protocols at different CT scanners (SOMATOM-Definition-AS+®(CT1) and SOMATOM-Definition-Flash® (CT2)) using two different lens-protection systems (Somatex® (SOM) and Medical Imaging Systems® (MIS)). Summarised percentage of the transmitted photons: (1) CT1 (a) unenhanced CT (nCT) with gantry angulation: SOM = 103%, MIS = 111%; (2) CT2 (a) nCT without gantry angulation: SOM = 81%, MIS = 91%; (b) CT angiography (CTA) with automatic dose-modulation technique: SOM = 39%, MIS = 74%; (c) CTA without dose-modulation technique: SOM = 22%, MIS = 48%; (d) CT perfusion: SOM = 44%, MIS = 69%. SOM showed a higher dose-reduction potential than MIS maintaining equal image quality. Lens-protection systems are most effective in CTA protocols without dose-reduction techniques. Lens-protection systems lower the average eye lens dose during CT scans up to 1/3 (MIS) and 2/3 (SOM), respectively, if the eye lens is exposed to the direct beam of radiation. Considering both the CT protocol and the material of lens protectors, they seem to be mandatory for reducing the radiation exposure of the eye lens. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

2017-10-01

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

Evaluation of adaptive treatment planning for patients with non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Zhong, Hualiang; Siddiqui, Salim M.; Movsas, Benjamin; Chetty, Indrin J.

2017-06-01

The purpose of this study was to develop metrics to evaluate uncertainties in deformable dose accumulation for patients with non-small cell lung cancer (NSCLC). Initial treatment plans (primary) and cone-beam CT (CBCT) images were retrospectively processed for seven NSCLC patients, who showed significant tumor regression during the course of treatment. Each plan was developed with IMRT for 2 Gy  ×  33 fractions. A B-spline-based DIR algorithm was used to register weekly CBCT images to a reference image acquired at fraction 21 and the resultant displacement vector fields (DVFs) were then modified using a finite element method (FEM). The doses were calculated on each of these CBCT images and mapped to the reference image using a tri-linear dose interpolation method, based on the B-spline and FEM-generated DVFs. Contours propagated from the planning image were adjusted to the residual tumor and OARs on the reference image to develop a secondary plan. For iso-prescription adaptive plans (relative to initial plans), mean lung dose (MLD) was reduced, on average from 17.3 Gy (initial plan) to 15.2, 14.5 and 14.8 Gy for the plans adapted using the rigid, B-Spline and FEM-based registrations. Similarly, for iso-toxic adaptive plans (considering MLD relative to initial plans) using the rigid, B-Spline and FEM-based registrations, the average doses were 69.9  ±  6.8, 65.7  ±  5.1 and 67.2  ±  5.6 Gy in the initial volume (PTV1), and 81.5  ±  25.8, 77.7  ±  21.6, and 78.9  ±  22.5 Gy in the residual volume (PTV21), respectively. Tumor volume reduction was correlated with dose escalation (for isotoxic plans, correlation coefficient  =  0.92), and with MLD reduction (for iso-fractional plans, correlation coefficient  =  0.85). For the case of the iso-toxic dose escalation, plans adapted with the B-Spline and FEM DVFs differed from the primary plan adapted with rigid registration by 2.8  ±  1.0 Gy and 1.8  ±  0.9 Gy in PTV1, and the mean difference between doses accumulated using the B-spline and FEM DVF’s was 1.1  ±  0.6 Gy. As a dose mapping-induced energy change, energy defect in the tumor volume was 20.8  ±  13.4% and 4.5  ±  2.4% for the B-spline and FEM-based dose accumulations, respectively. The energy defect of the B-Spline-based dose accumulation is significant in the tumor volume and highly correlated to the difference between the B-Spline and FEM-accumulated doses with their correlation coefficient equal to 0.79. Adaptive planning helps escalate target dose and spare normal tissue for patients with NSCLC, but deformable dose accumulation may have a significant loss of energy in regressed tumor volumes when using image intensity-based DIR algorithms. The metric of energy defect is a useful tool for evaluation of adaptive planning accuracy for lung cancer patients.

Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study.

PubMed

Somchit, Muhammad Nazrul; Mohamed, Nor Azura; Ahmad, Zuraini; Zakaria, Zainul Amiruddin; Shamsuddin, Lokman; Omar-Fauzee, Mohd Sofian; Kadir, Arifah Abdul

2014-09-01

Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.

Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study.

PubMed

Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie

2017-05-01

Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at aspirin without differentiation by dose. This is the first report to suggest that the reduction in risk occurs for low-dose aspirin and not for regular-dose aspirin and only among women with the hormone receptor-positive/HER2-negative subtype. This preliminary study builds on previous knowledge and further supports the need for formal cancer chemoprevention studies of low-dose aspirin.

Optimization of 64-MDCT urography: effect of dual-phase imaging with furosemide on collecting system opacification and radiation dose.

PubMed

Portnoy, Orith; Guranda, Larisa; Apter, Sara; Eiss, David; Amitai, Marianne Michal; Konen, Eli

2011-11-01

The purpose of this study was to compare opacification of the urinary collecting system and radiation dose associated with three-phase 64-MDCT urographic protocols and those associated with a split-bolus dual-phase protocol including furosemide. Images from 150 CT urographic examinations performed with three scanning protocols were retrospectively evaluated. Group A consisted of 50 sequentially registered patients who underwent a three-phase protocol with saline infusion. Group B consisted of 50 sequentially registered patients who underwent a reduced-radiation three-phase protocol with saline. Group C consisted of 50 sequentially registered patients who underwent a dual-phase split-bolus protocol that included a low-dose furosemide injection. Opacification of the urinary collecting system was evaluated with segmental binary scoring. Contrast artifacts were evaluated, and radiation doses were recorded. Results were compared by analysis of variance. A significant reduction in mean effective radiation dose was found between groups A and B (p < 0.001) and between groups B and C (p < 0.001), resulting in 65% reduction between groups A and C (p < 0.001). This reduction did not significantly affect opacification score in any of the 12 urinary segments (p = 0.079). In addition, dense contrast artifacts overlying the renal parenchyma observed with the three-phase protocols (groups A and B) were avoided with the dual-phase protocol (group C) (p < 0.001). A dual-phase protocol with furosemide injection is the preferable technique for CT urography. In comparison with commonly used three-phase protocols, the dual-phase protocol significantly reduces radiation exposure dose without reduction in image quality.

Paediatric dose reduction with the introduction of digital fluorography.

PubMed

Mooney, R B; McKinstry, J

2001-01-01

Fluoroscopy guided examinations in a paediatric X ray department were initially carried out on a unit that used a conventional screen-film combination for spot-films. A new fluoroscopy unit was installed with the facilities of digital fluorography and last image hold. Comparison of equipment performance showed that the dose per image for screen-film and digital fluorography was 3 microGy and 0.4 microGy, respectively. Although the screen-film had superior image quality, the department's radiologist confirmed that digital fluorography provided a diagnostic image. Patient dose measurements showed that introduction of the new unit caused doses to fall by an average of 70%, although fluoroscopy time had not changed significantly. The new unit produced 40% less air kerma during fluoroscopy. The remaining 30% reduction in dose was due to the introduction of digital fluorography and last image hold facilities. It is concluded that the use of digital fluorography can be an effective way of reducing paediatric dose.

[Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

PubMed

Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

1981-06-01

The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

Analysis of Radiation Transport Due to Activated Coolant in the ITER Neutral Beam Injection Cell

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

Royston, Katherine; Wilson, Stephen C.; Risner, Joel M.

Detailed spatial distributions of the biological dose rate due to a variety of sources are required for the design of the ITER tokamak facility to ensure that all radiological zoning limits are met. During operation, water in the Integrated loop of Blanket, Edge-localized mode and vertical stabilization coils, and Divertor (IBED) cooling system will be activated by plasma neutrons and will flow out of the bioshield through a complex system of pipes and heat exchangers. This paper discusses the methods used to characterize the biological dose rate outside the tokamak complex due to 16N gamma radiation emitted by the activatedmore » coolant in the Neutral Beam Injection (NBI) cell of the tokamak building. Activated coolant will enter the NBI cell through the IBED Primary Heat Transfer System (PHTS), and the NBI PHTS will also become activated due to radiation streaming through the NBI system. To properly characterize these gamma sources, the production of 16N, the decay of 16N, and the flow of activated water through the coolant loops were modeled. The impact of conservative approximations on the solution was also examined. Once the source due to activated coolant was calculated, the resulting biological dose rate outside the north wall of the NBI cell was determined through the use of sophisticated variance reduction techniques. The AutomateD VAriaNce reducTion Generator (ADVANTG) software implements methods developed specifically to provide highly effective variance reduction for complex radiation transport simulations such as those encountered with ITER. Using ADVANTG with the Monte Carlo N-particle (MCNP) radiation transport code, radiation responses were calculated on a fine spatial mesh with a high degree of statistical accuracy. In conclusion, advanced visualization tools were also developed and used to determine pipe cell connectivity, to facilitate model checking, and to post-process the transport simulation results.« less

Analysis of Radiation Transport Due to Activated Coolant in the ITER Neutral Beam Injection Cell

DOE PAGES

Royston, Katherine; Wilson, Stephen C.; Risner, Joel M.; ...

2017-07-26

Detailed spatial distributions of the biological dose rate due to a variety of sources are required for the design of the ITER tokamak facility to ensure that all radiological zoning limits are met. During operation, water in the Integrated loop of Blanket, Edge-localized mode and vertical stabilization coils, and Divertor (IBED) cooling system will be activated by plasma neutrons and will flow out of the bioshield through a complex system of pipes and heat exchangers. This paper discusses the methods used to characterize the biological dose rate outside the tokamak complex due to 16N gamma radiation emitted by the activatedmore » coolant in the Neutral Beam Injection (NBI) cell of the tokamak building. Activated coolant will enter the NBI cell through the IBED Primary Heat Transfer System (PHTS), and the NBI PHTS will also become activated due to radiation streaming through the NBI system. To properly characterize these gamma sources, the production of 16N, the decay of 16N, and the flow of activated water through the coolant loops were modeled. The impact of conservative approximations on the solution was also examined. Once the source due to activated coolant was calculated, the resulting biological dose rate outside the north wall of the NBI cell was determined through the use of sophisticated variance reduction techniques. The AutomateD VAriaNce reducTion Generator (ADVANTG) software implements methods developed specifically to provide highly effective variance reduction for complex radiation transport simulations such as those encountered with ITER. Using ADVANTG with the Monte Carlo N-particle (MCNP) radiation transport code, radiation responses were calculated on a fine spatial mesh with a high degree of statistical accuracy. In conclusion, advanced visualization tools were also developed and used to determine pipe cell connectivity, to facilitate model checking, and to post-process the transport simulation results.« less

A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose

PubMed Central

Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S

2014-01-01

Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447

Influence of a Commercial Lead Apron on Patient Skin Dose Delivered During Oral and Maxillofacial Examinations under Cone Beam Computed Tomography (CBCT).

PubMed

Schulze, Ralf Kurt Willy; Sazgar, Mahssa; Karle, Heiko; de Las Heras Gala, Hugo

2017-08-01

The purpose of this paper is to investigate the impact of a commercial lead apron on patient skin dose delivered during maxillofacial CBCT in five critical regions by means of solid-state-dosimetry. Five anatomical regions (thyroid gland, left and right breast, gonads, back of the phantom torso) in an adult female anthropomorphic phantom were selected for dose measurement by means of the highly sensitive solid-state dosimeter QUART didoSVM. Ten repeated single exposures were assessed for each patient body region for a total of five commercial CBCT devices with and without a lead apron present. Shielded and non-shielded exposures were compared under the paired Wilcoxon test, with absolute and relative differences computed. Reproducibility was expressed as the coefficient of variation (CV) between the 10 repeated assessments. The highest doses observed at skin level were found at the thyroid (mean shielded ± SD: 450.5 ± 346.7 μGy; non-shielded: 339.2 ± 348.8 μGy, p = 0.4922). Shielding resulted in a highly significant (p < 0.001) 93% dose reduction in skin dose in the female breast region with a mean non-shielded dose of approximately 35 μGy. Dose reduction was also significantly lower for the back-region (mean: -65%, p < 0.0001) as well as for the gonad-region (mean: -98%, p < 0.0001) in the shielded situation. Reproducibility was inversely correlated to skin dose (Rspearman = -0.748, p < 0.0001) with a mean CV of 10.45% (SD: 24.53 %). Skin dose in the thyroid region of the simulated patient was relatively high and not influenced by the lead apron, which did not shield this region. Dose reduction by means of a commercial lead apron was significant in all other regions, particularly in the region of the female breast.

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

2015-04-01

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

Guar gum and reduction of post-prandial glycaemia: effect of incorporation into solid food, liquid food, and both.

PubMed

Wolever, T M; Jenkins, D J; Nineham, R; Alberti, K G

1979-05-01

1. The influence of the dose and the form in which guar gum was given on the degree of "flattening" of blood glucose curves was studied in five subjects using meals of bread and soup containing 5 or 10 g guar gum. 2. When 5 g guar gum was added to bread the peak increase of blood glucose was reduced by 41% (P less than 0.002), with 5 g guar in soup, the reduction was 54% (P less than 0.001) while a reduction of 68% (P less than 0.001) was seen with 10 g guar gum (5 g in bread and 5 g in soup). The corresponding reduction in insulin peak increases were 37% (P less than 0.002), 50% (P less than 0.001) and 65% (P less than 0.001) respectively. 3. The difference between the two 5 g doses was significant with respect to the reduction of the peak increases in blood glucose and serum insulin; however the difference between the 5 g dose in bread and the 10 g dose was significantly different (P less than 0.02 for glucose, P less than 0.01 for insulin). 4. The results indicate that as little as 5 g guar gum may reduce the glycaemia following a 45 g carbohydrate meal, but perhaps due to earlier and more complete mixing, guar gum is most effective when added to the liquid phase of the meal.

Does Zika virus infection affect mosquito response to repellents?

PubMed Central

Leal, Walter S.; Barbosa, Rosângela M. R.; Zeng, Fangfang; Faierstein, Gabriel B.; Tan, Kaiming; Paiva, Marcelo H. S.; Guedes, Duschinka R. D.; Crespo, Mônica M.; Ayres, Constância F. J.

2017-01-01

The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject’s arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays. PMID:28205633

An agent-based model for control strategies of Echinococcus granulosus.

PubMed

Huang, Liang; Huang, Yan; Wang, Qian; Xiao, Ning; Yi, Deyou; Yu, Wenjie; Qiu, Dongchuan

2011-06-30

Cystic echinococcosis is a widespread zoonosis, caused by Echinococcus granulosus. The definitive hosts are carnivores and the intermediate hosts are grazing animals. Because humans are often accidentally infected with the cystic stage of the parasite, a control program is being developed for Western China. Western Sichuan Province in China is a highly endemic area. In this study, we built an agent-based model (ABM) to simulate and assess possible control strategies. These included dog dosing, control of livestock slaughter, health education, vaccination of intermediate hosts, vaccination of definitive hosts, slow-released praziquantel injections for dogs, removing unproductive old livestock, dog population reduction. These strategies were examined singly and in various combinations. The results show that vaccination based control strategies and also combined control strategies (dog dosing, slaughter control, removing old livestock, dog population reduction) can achieve a higher efficiency and be more feasible. Although monthly dog dosing achieved the highest efficiency, it required a high frequency and reliability, which were not feasible or sustainable. The model also indicated that transmission would recover soon after the chosen control strategy was stopped, indicating the need to move from a successful attack phase to a sustainable consolidation phase. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism.

PubMed

Wada, Hiromi

2017-03-01

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular aspect of silver nanoparticles regulated embryonic development in Zebrafish (Danio rerio) by Oct-4 expression.

PubMed

Sarkar, Biplab; Verma, Suresh K; Akhtar, Javed; Netam, Surya Prakash; Gupta, Sanjay Kr; Panda, Pritam Kumar; Mukherjee, Koel

2018-09-01

With the enhancement of commercial manifestation of silver nanoparticles, concerned has risen on their accumulation in aquatic system and consequent effects on fish development and metabolism. In this study, experiments were conducted to assess the impacts of silver nanoparticles on early life cycles of fish considering Zebrafish (Danio rerio) as experimental model. Silver nanoparticles were synthesized through chemical reduction method and characterized through UV-visible spectroscopy, dynamic light scattering (DLS), and HR-TEM. Different sub lethal doses of nanosilver were applied (13.6, 21.6, 42.4, 64, and 128 μgL -1 ) to post-fertilization phases of Zebrafish embryos and their interaction effects were monitored up to six days period. No significant morphological variations were observed at 13.6, 21.6, 42.4 μgL -1 dose of silver nanoparticles, whereas 64 and 128 μgL -1 exposure dose exhibited bending in myotome, deformity in tail region, somites, notochord and swelling in anterior and posterior region of embryos and larva. Hatching performances analysis elicited highest hatching success in 13.6 and 21.6 μgL -1 doses of silver nanoparticles followed by positive and negative control, whereas exposure dose of 64 and 128 μgL -1 exhibited comparatively lower success. Western blot analysis were conducted on developing hatchlings with Oct4 antibody and at 13.6 and 21.6 μgL -1 dose,it showed over expression elucidating stimulatory role of nanosilver in these mentioned doses. In silico analysis depicted a firm interaction of nanosilver with Oct4 revealing their key role in growth stimulation of developing embryos. The study demonstrates the function of nanosilver as a growth promoter rather only as a toxicant in fish metabolic system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dose and scatter characteristics of a novel cone beam CT system for musculoskeletal extremities

NASA Astrophysics Data System (ADS)

Zbijewski, W.; Sisniega, A.; Vaquero, J. J.; Muhit, A.; Packard, N.; Senn, R.; Yang, D.; Yorkston, J.; Carrino, J. A.; Siewerdsen, J. H.

2012-03-01

A novel cone-beam CT (CBCT) system has been developed with promising capabilities for musculoskeletal imaging (e.g., weight-bearing extremities and combined radiographic / volumetric imaging). The prototype system demonstrates diagnostic-quality imaging performance, while the compact geometry and short scan orbit raise new considerations for scatter management and dose characterization that challenge conventional methods. The compact geometry leads to elevated, heterogeneous x-ray scatter distributions - even for small anatomical sites (e.g., knee or wrist), and the short scan orbit results in a non-uniform dose distribution. These complex dose and scatter distributions were investigated via experimental measurements and GPU-accelerated Monte Carlo (MC) simulation. The combination provided a powerful basis for characterizing dose distributions in patient-specific anatomy, investigating the benefits of an antiscatter grid, and examining distinct contributions of coherent and incoherent scatter in artifact correction. Measurements with a 16 cm CTDI phantom show that the dose from the short-scan orbit (0.09 mGy/mAs at isocenter) varies from 0.16 to 0.05 mGy/mAs at various locations on the periphery (all obtained at 80 kVp). MC estimation agreed with dose measurements within 10-15%. Dose distribution in patient-specific anatomy was computed with MC, confirming such heterogeneity and highlighting the elevated energy deposition in bone (factor of ~5-10) compared to soft-tissue. Scatter-to-primary ratio (SPR) up to ~1.5-2 was evident in some regions of the knee. A 10:1 antiscatter grid was found earlier to result in significant improvement in soft-tissue imaging performance without increase in dose. The results of MC simulations elucidated the mechanism behind scatter reduction in the presence of a grid. A ~3-fold reduction in average SPR was found in the MC simulations; however, a linear grid was found to impart additional heterogeneity in the scatter distribution, mainly due to the increase in the contribution of coherent scatter with increased spatial variation. Scatter correction using MC-generated scatter distributions demonstrated significant improvement in cupping and streaks. Physical experimentation combined with GPU-accelerated MC simulation provided a sophisticated, yet practical approach in identifying low-dose acquisition techniques, optimizing scatter correction methods, and evaluating patientspecific dose.

Neutron organ dose and the influence of adipose tissue

NASA Astrophysics Data System (ADS)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

PubMed Central

Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

2016-01-01

Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

Facilitating the implementation of pharmacokinetic-guided dosing of prophylaxis in haemophilia care by discrete choice experiment.

PubMed

Lock, J; de Bekker-Grob, E W; Urhan, G; Peters, M; Meijer, K; Brons, P; van der Meer, F J M; Driessens, M H E; Collins, P W; Fijnvandraat, K; Leebeek, F W G; Cnossen, M H

2016-01-01

Patients', parents' and providers' preferences with regard to medical innovations may have a major impact on their implementation. To evaluate barriers and facilitators for individualized pharmacokinetic (PK)-guided dosing of prophylaxis in haemophilia patients, parents of young patients, and treating professionals by discrete choice experiment (DCE) questionnaire. The study population consisted of patients with haemophilia currently or previously on prophylactic treatment with factor concentrate (n = 114), parents of patients aged 12-18 years (n = 19) and haemophilia professionals (n = 91). DCE data analysis was performed, taking preference heterogeneity into account. Overall, patients and parents, and especially professionals were inclined to opt for PK-guided dosing of prophylaxis. In addition, if bleeding was consequently reduced, more frequent infusions were acceptable. However, daily dosing remained an important barrier for all involved. 'Reduction of costs for society' was a facilitator for implementation in all groups. To achieve implementation of individualized PK-guided dosing of prophylaxis in haemophilia, reduction of bleeding risk and reduction of costs for society should be actively discussed as they are motivating for implementation; daily dosing is still reported to be a barrier for all groups. The knowledge of these preferences will enlarge support for this innovation, and aid in the drafting of implementable guidelines and information brochures for patients, parents and professionals. © 2015 John Wiley & Sons Ltd.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

PubMed

Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel

2016-06-01

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

PubMed

Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J

2017-05-01

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

[Adherence of type 2 diabetes patients on insulin analogues application: missed dose, time imprecision and dose reduction. The results of GAPP2TM(Global Attitudes of Physicians and Patient) survey in the Czech Republic].

PubMed

Prázný, Martin

2014-11-01

Irregular insulin dose is one of the main problems associated with insulin therapy in patients with type 2 diabetes; its extent is not known precisely. The aim of survey conducted in the Czech Republic in the international project GAPP2 - Global Attitudes of Patients and Physicians was to determine the incidence and the impact of irregular use of basal insulin analogues in patients with type 2 diabetes, to point out the reasons for these irregularities and to focus on how physicians discuss irregular application of insulin with patients. The project GAPP2 is an international cross-sectional study performed on-line via the Internet using a questionnaire filled by diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was conducted in two steps in 17 countries; the first step included 6 countries and was completed in the beginning of 2012, the second step involved 11 other countries including the Czech Republic with termination in 2014. The survey was designed to obtain the views of patients and physicians on certain aspects of insulin treatment and persistent issues in this field in the real daily practice. Special focus was on the incidence and management of hypoglycaemia as well as on irregularities of insulin application. In the part dedicated to adherence to basal insulin application were observed three types of irregular insulin therapy: missed dose, time imprecision of dose (± 2 hours vs. the prescribed time) and dose reduction in all cases in the past 30 days before completing the questionnaire. In addition, it was investigated the attitude and relation of patients to these issues. The results have shown that irregular insulin dose in the Czech Republic is less frequent than in other countries involved in the GAPP2 research. Nevertheless, approximately one fifth of diabetic patients using insulin analogues in basal-bolus or only basal therapy regimen is related to this problem. The last irregular insulin application was due to missed dose in 13% of cases, time imprecision in 23% and reduction of dose in 61% of cases. The most commonly reported reason was risk reduction of hypoglycaemia and the recommendations of health professionals. Fear of missed dose is present in 40% Czech patients and 35% would feel guilty if their insulin dose is missed (up to 47% in patients with intensified insulin regimen). Only 60% patients are aware of negative impact on their long-term health after missed dose of basal insulin. Questioned doctors have suspected that the patients report lower number of missed doses during regular medical check because one third of patients doesn´t admit missed dose. However, this fact conceded only 11% of patients on basal insulin and 15% of patients on intensified insulin therapy. Quarter of prescribing doctors admit that they usually don´t discuss with patients irregularities in basal insulin treatment. Although, type 2 diabetes patients in the Czech Republic follow prescribed basal insulin therapy scheme more often than patients in other countries participating in the survey GAPP2 , missed dose, time imprecision and reduction of dose is quite common and it deserves more attention from medical side during regular medical check together with appropriate education of patients.

Development of adaptive noise reduction filter algorithm for pediatric body images in a multi-detector CT

NASA Astrophysics Data System (ADS)

Nishimaru, Eiji; Ichikawa, Katsuhiro; Okita, Izumi; Ninomiya, Yuuji; Tomoshige, Yukihiro; Kurokawa, Takehiro; Ono, Yutaka; Nakamura, Yuko; Suzuki, Masayuki

2008-03-01

Recently, several kinds of post-processing image filters which reduce the noise of computed tomography (CT) images have been proposed. However, these image filters are mostly for adults. Because these are not very effective in small (< 20 cm) display fields of view (FOV), we cannot use them for pediatric body images (e.g., premature babies and infant children). We have developed a new noise reduction filter algorithm for pediatric body CT images. This algorithm is based on a 3D post-processing in which the output pixel values are calculated by nonlinear interpolation in z-directions on original volumetric-data-sets. This algorithm does not need the in-plane (axial plane) processing, so the spatial resolution does not change. From the phantom studies, our algorithm could reduce SD up to 40% without affecting the spatial resolution of x-y plane and z-axis, and improved the CNR up to 30%. This newly developed filter algorithm will be useful for the diagnosis and radiation dose reduction of the pediatric body CT images.

Peak skin and eye lens radiation dose from brain perfusion CT based on Monte Carlo simulation.

PubMed

Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Stevens, Donna M; Zankl, Maria; Demarco, John J; Turner, Adam C; Khatonabadi, Maryam; McNitt-Gray, Michael F

2012-02-01

The purpose of our study was to accurately estimate the radiation dose to skin and the eye lens from clinical CT brain perfusion studies, investigate how well scanner output (expressed as volume CT dose index [CTDI(vol)]) matches these estimated doses, and investigate the efficacy of eye lens dose reduction techniques. Peak skin dose and eye lens dose were estimated using Monte Carlo simulation methods on a voxelized patient model and 64-MDCT scanners from four major manufacturers. A range of clinical protocols was evaluated. CTDI(vol) for each scanner was obtained from the scanner console. Dose reduction to the eye lens was evaluated for various gantry tilt angles as well as scan locations. Peak skin dose and eye lens dose ranged from 81 mGy to 348 mGy, depending on the scanner and protocol used. Peak skin dose and eye lens dose were observed to be 66-79% and 59-63%, respectively, of the CTDI(vol) values reported by the scanners. The eye lens dose was significantly reduced when the eye lenses were not directly irradiated. CTDI(vol) should not be interpreted as patient dose; this study has shown it to overestimate dose to the skin or eye lens. These results may be used to provide more accurate estimates of actual dose to ensure that protocols are operated safely below thresholds. Tilting the gantry or moving the scanning region further away from the eyes are effective for reducing lens dose in clinical practice. These actions should be considered when they are consistent with the clinical task and patient anatomy.

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Patient-specific dose estimation for pediatric chest CT

PubMed Central

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2008-01-01

Current methods for organ and effective dose estimations in pediatric CT are largely patient generic. Physical phantoms and computer models have only been developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10, 15years old) and do not reflect the variability of patient anatomy and body habitus within the same size/age group. In this investigation, full-body computer models of seven pediatric patients in the same size/protocol group (weight: 11.9–18.2kg) were created based on the patients’ actual multi-detector array CT (MDCT) data. Organs and structures in the scan coverage were individually segmented. Other organs and structures were created by morphing existing adult models (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. Organ and effective dose of these patients from a chest MDCT scan protocol (64 slice LightSpeed VCT scanner, 120kVp, 70 or 75mA, 0.4s gantry rotation period, pitch of 1.375, 20mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated to simulate radiation transport in the same CT system. The seven patients had normalized effective dose of 3.7–5.3mSv∕100mAs (coefficient of variation: 10.8%). Normalized lung dose and heart dose were 10.4–12.6mGy∕100mAs and 11.2–13.3mGy∕100mAs, respectively. Organ dose variations across the patients were generally small for large organs in the scan coverage (<7%), but large for small organs in the scan coverage (9%–18%) and for partially or indirectly exposed organs (11%–77%). Normalized effective dose correlated weakly with body weight (correlation coefficient:r=−0.80). Normalized lung dose and heart dose correlated strongly with mid-chest equivalent diameter (lung: r=−0.99, heart: r=−0.93); these strong correlation relationships can be used to estimate patient-specific organ dose for any other patient in the same size/protocol group who undergoes the chest scan. In summary, this work reported the first assessment of dose variations across pediatric CT patients in the same size/protocol group due to the variability of patient anatomy and body habitus and provided a previously unavailable method for patient-specific organ dose estimation, which will help in assessing patient risk and optimizing dose reduction strategies, including the development of scan protocols. PMID:19175138

Patient-specific dose estimation for pediatric chest CT

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

Li Xiang; Samei, Ehsan; Segars, W. Paul

2008-12-15

Current methods for organ and effective dose estimations in pediatric CT are largely patient generic. Physical phantoms and computer models have only been developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10, 15 years old) and do not reflect the variability of patient anatomy and body habitus within the same size/age group. In this investigation, full-body computer models of seven pediatric patients in the same size/protocol group (weight: 11.9-18.2 kg) were created based on the patients' actual multi-detector array CT (MDCT) data. Organs and structures in the scan coverage were individually segmented. Other organs and structuresmore » were created by morphing existing adult models (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. Organ and effective dose of these patients from a chest MDCT scan protocol (64 slice LightSpeed VCT scanner, 120 kVp, 70 or 75 mA, 0.4 s gantry rotation period, pitch of 1.375, 20 mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated to simulate radiation transport in the same CT system. The seven patients had normalized effective dose of 3.7-5.3 mSv/100 mAs (coefficient of variation: 10.8%). Normalized lung dose and heart dose were 10.4-12.6 mGy/100 mAs and 11.2-13.3 mGy/100 mAs, respectively. Organ dose variations across the patients were generally small for large organs in the scan coverage (<7%), but large for small organs in the scan coverage (9%-18%) and for partially or indirectly exposed organs (11%-77%). Normalized effective dose correlated weakly with body weight (correlation coefficient: r=-0.80). Normalized lung dose and heart dose correlated strongly with mid-chest equivalent diameter (lung: r=-0.99, heart: r=-0.93); these strong correlation relationships can be used to estimate patient-specific organ dose for any other patient in the same size/protocol group who undergoes the chest scan. In summary, this work reported the first assessment of dose variations across pediatric CT patients in the same size/protocol group due to the variability of patient anatomy and body habitus and provided a previously unavailable method for patient-specific organ dose estimation, which will help in assessing patient risk and optimizing dose reduction strategies, including the development of scan protocols.« less

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

[Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

PubMed

Zhou, Rong-Yi; Wang, Jiao-Jiao; You, Yue; Sun, Ji-Chao; Song, Yu-Chen; Yuan, Hai-Xia; Han, Xin-Min

2017-05-01

To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05). Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy.

PubMed

Holl, Katsiaryna; Sauboin, Christophe; Amodio, Emanuele; Bonanni, Paolo; Gabutti, Giovanni

2016-10-21

Varicella is a highly infectious disease with a significant public health and economic burden, which can be prevented with childhood routine varicella vaccination. Vaccination strategies differ by country. Some factors are known to play an important role (number of doses, coverage, dosing interval, efficacy and catch-up programmes), however, their relative impact on the reduction of varicella in the population remains unclear. This paper aims to help policy makers prioritise the critical factors to achieve the most successful vaccination programme with the available budget. Scenarios assessed the impact of different vaccination strategies on reduction of varicella disease in the population. A dynamic transmission model was used and adapted to fit Italian demographics and population mixing patterns. Inputs included coverage, number of doses, dosing intervals, first-dose efficacy and availability of catch-up programmes, based on strategies currently used or likely to be used in different countries. The time horizon was 30 years. Both one- and two-dose routine varicella vaccination strategies prevented a comparable number of varicella cases with complications, but two-doses provided broader protection due to prevention of a higher number of milder varicella cases. A catch-up programme in susceptible adolescents aged 10-14 years old reduced varicella cases by 27-43 % in older children, which are often more severe than in younger children. Coverage, for all strategies, sustained at high levels achieved the largest reduction in varicella. In general, a 20 % increase in coverage resulted in a further 27-31 % reduction in varicella cases. When high coverage is reached, the impact of dosing interval and first-dose vaccine efficacy had a relatively lower impact on disease prevention in the population. Compared to the long (11 years) dosing interval, the short (5 months) and medium (5 years) interval schedules reduced varicella cases by a further 5-13 % and 2-5 %, respectively. Similarly, a 10 % increase in first-dose efficacy (from 65 to 75 % efficacy) prevented 2-5 % more varicella cases, suggesting it is the least influential factor when considering routine varicella vaccination. Vaccination strategies can be implemented differently in each country depending on their needs, infrastructure and healthcare budget. However, ensuring high coverage remains the critical success factor for significant prevention of varicella when introducing varicella vaccination in the national immunisation programme.

The diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients: A systematic review and diagnostic meta-analysis.

PubMed

Yoon, Hee Mang; Suh, Chong Hyun; Cho, Young Ah; Kim, Jeong Rye; Lee, Jin Seong; Jung, Ah Young; Kim, Jung Heon; Lee, Jeong-Yong; Kim, So Yeon

2018-06-01

To evaluate the diagnostic performance of reduced-dose CT for suspected appendicitis. A systematic search of the MEDLINE and EMBASE databases was carried out through to 10 January 2017. Studies evaluating the diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients were selected. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modelling. Meta-regression was performed. Fourteen original articles with a total of 3,262 patients were included. For all studies using reduced-dose CT, the summary sensitivity was 96 % (95 % CI 93-98) with a summary specificity of 94 % (95 % CI 92-95). For the 11 studies providing a head-to-head comparison between reduced-dose CT and standard-dose CT, reduced-dose CT demonstrated a comparable summary sensitivity of 96 % (95 % CI 91-98) and specificity of 94 % (95 % CI 93-96) without any significant differences (p=.41). In meta-regression, there were no significant factors affecting the heterogeneity. The median effective radiation dose of the reduced-dose CT was 1.8 mSv (1.46-4.16 mSv), which was a 78 % reduction in effective radiation dose compared to the standard-dose CT. Reduced-dose CT shows excellent diagnostic performance for suspected appendicitis. • Reduced-dose CT shows excellent diagnostic performance for evaluating suspected appendicitis. • Reduced-dose CT has a comparable diagnostic performance to standard-dose CT. • Median effective radiation dose of reduced-dose CT was 1.8 mSv (1.46-4.16). • Reduced-dose CT achieved a 78 % dose reduction compared to standard-dose CT.

Effects of Three Low-Doses of D-Tagatose on Glycemic Control Over Six Months in Subjects with Mild Type 2 Diabetes Mellitus Under Control with Diet and Exercise.

PubMed

Ensor, Mark; Williams, Jarrod; Smith, Rebecca; Banfield, Amy; Lodder, Robert A

2014-10-01

The primary objective of this study was to evaluate the safety and the effect of D-tagatose on the glycemic control of subjects with type 2 diabetes as determined by HbA 1c levels at the end of 6 months of therapy using the subject's own baseline HbA 1c level as a comparator. The determination of the minimal dose required to cause a statistically significant reduction in HbA 1c was of particular interest. Eight weeks after screening, the qualifying subjects were randomized to receive one of three doses of D-tagatose: 2.5 g TID, 5.0 g TID or 7.5 g TID. Blood levels of HbA 1c , fasting blood glucose concentrations, plasma lipids, changes in body weight, changes in body mass index, and change in insulin levels were checked at each study visit and at the end of the study. Treatment success, as measured by the reduction of HbA 1c , was greatest for the 7.5 g D-tagatose dose group, although the difference between the treatments was not statistically significant. For fasting glucose, only the 7.5 g dosage group exhibited reductions from baseline at the 3- and 6-month time points. Mean body weights reduced in a dose-response fashion, with the 5.0 g and the 7.5 g D-tagatose doses providing the greatest reductions. D-tagatose at dosages of 2.5 g, 5.0 g, and 7.5 g TID for six months were well tolerated by this subject population. D-tagatose at 5.0 g TID was the minimal dose required to reduce HbA 1c . D-tagatose at 7.5 g TID provided the greatest effect in most measured efficacy parameters.

Effects of Three Low-Doses of D-Tagatose on Glycemic Control Over Six Months in Subjects with Mild Type 2 Diabetes Mellitus Under Control with Diet and Exercise

PubMed Central

Ensor, Mark; Williams, Jarrod; Smith, Rebecca; Banfield, Amy; Lodder, Robert A.

2014-01-01

The primary objective of this study was to evaluate the safety and the effect of D-tagatose on the glycemic control of subjects with type 2 diabetes as determined by HbA1c levels at the end of 6 months of therapy using the subject’s own baseline HbA1c level as a comparator. The determination of the minimal dose required to cause a statistically significant reduction in HbA1c was of particular interest. Eight weeks after screening, the qualifying subjects were randomized to receive one of three doses of D-tagatose: 2.5 g TID, 5.0 g TID or 7.5 g TID. Blood levels of HbA1c, fasting blood glucose concentrations, plasma lipids, changes in body weight, changes in body mass index, and change in insulin levels were checked at each study visit and at the end of the study. Treatment success, as measured by the reduction of HbA1c, was greatest for the 7.5 g D-tagatose dose group, although the difference between the treatments was not statistically significant. For fasting glucose, only the 7.5 g dosage group exhibited reductions from baseline at the 3- and 6-month time points. Mean body weights reduced in a dose-response fashion, with the 5.0 g and the 7.5 g D-tagatose doses providing the greatest reductions. D-tagatose at dosages of 2.5 g, 5.0 g, and 7.5 g TID for six months were well tolerated by this subject population. D-tagatose at 5.0 g TID was the minimal dose required to reduce HbA1c. D-tagatose at 7.5 g TID provided the greatest effect in most measured efficacy parameters. PMID:25580449

Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics

PubMed Central

Tsuji, Brian T; Harigaya, Yoriko; Lesse, Alan J; Forrest, Alan; Ngo, Dung

2013-01-01

AFN-1252, a potent enoyl-ACP reductase (FabI) inhibitor, is under development for the treatment of Staphylococcus aureus infections. The activity of AFN-1252 against two isolates of S. aureus, MSSA 26213 and MRSA S186, was studied in an in vitro pharmacodynamic model simulating AFN-1252 pharmacokinetics in man. Reductions in bacterial viable count over the first 6 hours were generally 1–2 logs and maximal reductions in viable count were generally achieved at fAUC/MIC ratios of 100–200. Maximum reductions in viable count against MSSA 29213 and MRSA S186 were approximately 4 logs, achieved by 450 mg q12h (fAUC/MIC = 1875) dosing at 28 hours. Staphylococcal resistance to AFN-1252 did not develop throughout the 48-hour experiments. As multidrug resistance continues to increase, these studies support the continued investigation of AFN-1252 as a targeted therapeutic for staphylococcal infections. PMID:23433442

Periradicular Infiltration of the Cervical Spine: How New CT Scanner Techniques and Protocol Modifications Contribute to the Achievement of Low-Dose Interventions.

PubMed

Elsholtz, Fabian Henry Jürgen; Kamp, Julia Evi-Katrin; Vahldiek, Janis Lucas; Hamm, Bernd; Niehues, Stefan Markus

2018-06-18

 CT-guided periradicular infiltration of the cervical spine is an effective symptomatic treatment in patients with radiculopathy-associated pain syndromes. This study evaluates the robustness and safety of a low-dose protocol on a CT scanner with iterative reconstruction software.  A total of 183 patients who underwent periradicular infiltration therapy of the cervical spine were included in this study. 82 interventions were performed on a new CT scanner with a new intervention protocol using an iterative reconstruction algorithm. Spot scanning was implemented for planning and a basic low-dose setup of 80 kVp and 5 mAs was established during intermittent fluoroscopy. The comparison group included 101 prior interventions on a scanner without iterative reconstruction. The dose-length product (DLP), number of acquisitions, pain reduction on a numeric analog scale, and protocol changes to achieve a safe intervention were recorded.  The median DLP for the whole intervention was 24.3 mGy*cm in the comparison group and 1.8 mGy*cm in the study group. The median pain reduction was -3 in the study group and -2 in the comparison group. A 5 mAs increase in the tube current-time product was required in 5 patients of the study group.  Implementation of a new scanner and intervention protocol resulted in a 92.6 % dose reduction without a compromise in safety and pain relief. The dose needed here is more than 75 % lower than doses used for similar interventions in published studies. An increase of the tube current-time product was needed in only 6 % of interventions.   · The presented ultra-low-dose protocol allows for a significant dose reduction without compromising outcome.. · The protocol includes spot scanning for planning purposes and a basic setup of 80 kVp and 5 mAs.. · The iterative reconstruction algorithm is activated during fluoroscopy.. · Elsholtz FH, Kamp JE, Vahldiek JL et al. Periradicular Infiltration of the Cervical Spine: How New CT Scanner Techniques and Protocol Modifications Contribute to the Achievement of Low-Dose Interventions. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0632-3930. © Georg Thieme Verlag KG Stuttgart · New York.

Implementing smart infusion pumps with dose-error reduction software: real-world experiences.

PubMed

Heron, Claire

2017-04-27

Intravenous (IV) drug administration, especially with 'smart pumps', is complex and susceptible to errors. Although errors can occur at any stage of the IV medication process, most errors occur during reconstitution and administration. Dose-error reduction software (DERS) loaded on to infusion pumps incorporates a drug library with predefined upper and lower drug dose limits and infusion rates, which can reduce IV infusion errors. Although this is an important advance for patient safety at the point of care, uptake is still relatively low. This article discuses the challenges and benefits of implementing DERS in clinical practice as experienced by three UK trusts.

Low-dose dual-energy electronic cleansing for fecal-tagging CT Colonography

NASA Astrophysics Data System (ADS)

Cai, Wenli; Zhang, Da; Lee, June-Goo; Yoshida, Hiroyuki

2013-03-01

Dual-energy electronic cleansing (DE-EC) provides a promising means for cleansing the tagged fecal materials in fecaltagging CT colonography (CTC). However, the increased radiation dose due to the double exposures in dual-energy CTC (DE-CTC) scanning is a major limitation for the use of DE-EC in clinical practice. The purpose of this study was to develop and evaluate a low-dose DE-EC scheme in fecal-tagging DE-CTC. In this study, a custom-made anthropomorphic colon phantom, which was filled with simulated tagged materials by non-ionic iodinated contrast agent (Omnipaque iohexol, GE Healthcare), was scanned by a dual-source CT scanner (SOMATON Definition Flash, Siemens Healthcare) at two photon energies: 80 kVp and 140 kVp with nine different tube current settings ranging from 12 to 74 mAs for 140 kVp, and then reconstructed by soft-tissue reconstruction kernel (B30f). The DE-CTC images were subjected to a low-dose DE-EC scheme. First, our image-space DE-CTC denoising filter was applied for reduction of image noise. Then, the noise-reduced images were processed by a virtual lumen tagging method for reduction of partial volume effect and tagging inhomogeneity. The results were compared with the registered CTC images of native phantom without fillings. Preliminary results showed that our low-dose DE-EC scheme achieved the cleansing ratios, defined by the proportion of the cleansed voxels in the tagging mask, between 93.18% (12 mAs) and 96.62% (74 mAs). Also, the soft-tissue preservation ratios, defined by the proportion of the persevered voxels in the soft-tissue mask, were maintained in the range between 94.67% and 96.41%.

Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.

PubMed

Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugrešić, Nenad; Stepanović-Petrović, Radica

2015-07-01

Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

PubMed Central

Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

2016-01-01

Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

PubMed Central

Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

2016-01-01

Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestine

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

PubMed

Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

2016-07-01

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestine

Association of reduction of AFB1-induced liver tumours by antioxidants with increased activity of microsomal enzymes.

PubMed

Nyandieka, H S; Wakhis, J; Kilonzo, M M

1990-10-01

The influence of nutritional factors on aflatoxin B1 (AFB1)-induced liver tumours was investigated in rats. When a dose of 500 micrograms AFB1/kg body weight was given to rats in the absence of any anticarcinogen, 80 per cent of the rats developed liver tumours as compared to 0 to 40 per cent in those which received anticarcinogens. While beta-carotene totally inhibited the development of liver tumours ascorbic acid, selenium, and uric acid reduced the percentages of tumour-bearing rats to 13 per cent each. GSH and vitamin E also reduced these percentages to 20 and 40 per cent respectively. The reduction of tumour incidence by each anticarcinogen was associated with induction of increased microsomal enzyme activity. Inhibition of AFB1-induced liver cancer development thus seems to occur through microsomal enzyme induction and AFB1 activation.

ICRP publication 121: radiological protection in paediatric diagnostic and interventional radiology.

PubMed

Khong, P-L; Ringertz, H; Donoghue, V; Frush, D; Rehani, M; Appelgate, K; Sanchez, R

2013-04-01

Paediatric patients have a higher average risk of developing cancer compared with adults receiving the same dose. The longer life expectancy in children allows more time for any harmful effects of radiation to manifest, and developing organs and tissues are more sensitive to the effects of radiation. This publication aims to provide guiding principles of radiological protection for referring clinicians and clinical staff performing diagnostic imaging and interventional procedures for paediatric patients. It begins with a brief description of the basic concepts of radiological protection, followed by the general aspects of radiological protection, including principles of justification and optimisation. Guidelines and suggestions for radiological protection in specific modalities - radiography and fluoroscopy, interventional radiology, and computed tomography - are subsequently covered in depth. The report concludes with a summary and recommendations. The importance of rigorous justification of radiological procedures is emphasised for every procedure involving ionising radiation, and the use of imaging modalities that are non-ionising should always be considered. The basic aim of optimisation of radiological protection is to adjust imaging parameters and institute protective measures such that the required image is obtained with the lowest possible dose of radiation, and that net benefit is maximised to maintain sufficient quality for diagnostic interpretation. Special consideration should be given to the availability of dose reduction measures when purchasing new imaging equipment for paediatric use. One of the unique aspects of paediatric imaging is with regards to the wide range in patient size (and weight), therefore requiring special attention to optimisation and modification of equipment, technique, and imaging parameters. Examples of good radiographic and fluoroscopic technique include attention to patient positioning, field size and adequate collimation, use of protective shielding, optimisation of exposure factors, use of pulsed fluoroscopy, limiting fluoroscopy time, etc. Major paediatric interventional procedures should be performed by experienced paediatric interventional operators, and a second, specific level of training in radiological protection is desirable (in some countries, this is mandatory). For computed tomography, dose reduction should be optimised by the adjustment of scan parameters (such as mA, kVp, and pitch) according to patient weight or age, region scanned, and study indication (e.g. images with greater noise should be accepted if they are of sufficient diagnostic quality). Other strategies include restricting multiphase examination protocols, avoiding overlapping of scan regions, and only scanning the area in question. Up-to-date dose reduction technology such as tube current modulation, organ-based dose modulation, auto kV technology, and iterative reconstruction should be utilised when appropriate. It is anticipated that this publication will assist institutions in encouraging the standardisation of procedures, and that it may help increase awareness and ultimately improve practices for the benefit of patients. Copyright © 2012. Published by Elsevier Ltd.

Generalizable Class Solutions for Treatment Planning of Spinal Stereotactic Body Radiation Therapy

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

Weksberg, David C.; Palmer, Matthew B.; Vu, Khoi N.

2012-11-01

Purpose: Spinal stereotactic body radiation therapy (SBRT) continues to emerge as an effective therapeutic approach to spinal metastases; however, treatment planning and delivery remain resource intensive at many centers, which may hamper efficient implementation in clinical practice. We sought to develop a generalizable class solution approach for spinal SBRT treatment planning that would allow confidence that a given plan provides optimal target coverage, reduce integral dose, and maximize planning efficiency. Methods and Materials: We examined 91 patients treated with spinal SBRT at our institution. Treatment plans were categorized by lesion location, clinical target volume (CTV) configuration, and dose fractionation scheme,more » and then analyzed to determine the technically achievable dose gradient. A radial cord expansion was subtracted from the CTV to yield a planning CTV (pCTV) construct for plan evaluation. We reviewed the treatment plans with respect to target coverage, dose gradient, integral dose, conformality, and maximum cord dose to select the best plans and develop a set of class solutions. Results: The class solution technique generated plans that maintained target coverage and improved conformality (1.2-fold increase in the 95% van't Riet Conformation Number describing the conformality of a reference dose to the target) while reducing normal tissue integral dose (1.3-fold decrease in the volume receiving 4 Gy (V{sub 4Gy}) and machine output (19% monitor unit (MU) reduction). In trials of planning efficiency, the class solution technique reduced treatment planning time by 30% to 60% and MUs required by {approx}20%: an effect independent of prior planning experience. Conclusions: We have developed a set of class solutions for spinal SBRT that incorporate a pCTV metric for plan evaluation while yielding dosimetrically superior treatment plans with increased planning efficiency. Our technique thus allows for efficient, reproducible, and high-quality spinal SBRT treatment planning.« less

Technological advances in hybrid imaging and impact on dose.

PubMed

Mattsson, Sören; Andersson, Martin; Söderberg, Marcus

2015-07-01

New imaging technologies utilising X-rays and radiopharmaceuticals have developed rapidly. Clinical application of computed tomography (CT) has revolutionised medical imaging and plays an enormous role in medical care. Due to technical improvements, spatial, contrast and temporal resolutions have continuously improved. In spite of significant reduction of CT doses during recent years, CT is still a dominating source of radiation exposure to the population. Combinations with single photon emission computed tomography (SPECT) and positron emission tomography (PET) and especially the use of SPECT/CT and PET/CT, provide important additional information about physiology as well as cellular and molecular events. However, significant dose contributions from SPECT and PET occur, making PET/CT and SPECT/CT truly high dose procedures. More research should be done to find optimal activities of radiopharmaceuticals for various patient groups and investigations. The implementation of simple protocol adjustments, including individually based administration, encouraged hydration, forced diuresis and use of optimised voiding intervals, laxatives, etc., can reduce the radiation exposure to the patients. New data about staff doses to fingers, hands and eye lenses indicate that finger doses could be a problem, but not doses to the eye lenses and to the whole body. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neutron track length estimator for GATE Monte Carlo dose calculation in radiotherapy.

PubMed

Elazhar, H; Deschler, T; Létang, J M; Nourreddine, A; Arbor, N

2018-06-20

The out-of-field dose in radiation therapy is a growing concern in regards to the late side-effects and secondary cancer induction. In high-energy x-ray therapy, the secondary neutrons generated through photonuclear reactions in the accelerator are part of this secondary dose. The neutron dose is currently not estimated by the treatment planning system while it appears to be preponderant for distances greater than 50 cm from the isocenter. Monte Carlo simulation has become the gold standard for accurately calculating the neutron dose under specific treatment conditions but the method is also known for having a slow statistical convergence, which makes it difficult to be used on a clinical basis. The neutron track length estimator, a neutron variance reduction technique inspired by the track length estimator method has thus been developped for the first time in the Monte Carlo code GATE to allow a fast computation of the neutron dose in radiotherapy. The details of its implementation, as well as the comparison of its performances against the analog MC method, are presented here. A gain of time from 15 to 400 can be obtained by our method, with a mean difference in the dose calculation of about 1% in comparison with the analog MC method.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

PubMed

Richardson, Danielle; Poirier, Valerie J; Matsuyama, Arata; Calvalido, Jerome

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m 2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P < .0001) than dogs >10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P < .0001) than dogs >15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

Treatment of Fabry Disease: Outcome of a Comparative Trial with Agalsidase Alfa or Beta at a Dose of 0.2 mg/kg

PubMed Central

Vedder, Anouk C.; Linthorst, Gabor E.; Houge, Gunnar; Groener, Johannna E.M.; Ormel, Els E.; Bouma, Berto J.; Aerts, Johannes M.F.G.; Hirth, Asle; Hollak, Carla E.M.

2007-01-01

Background Two different enzyme preparations, agalsidase alfa (ReplagalTM, Shire) and beta (FabrazymeTM, Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial. Methodology/Principal Findings Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; χ2 = 0.38 p = 0.54. Conclusion Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease. Trial Registration International Standard Randomized Clinical Trial ISRCTN45178534 PMID:17622343

Allopurinol might improve response to azathioprine and 6-mercaptopurine by correcting an unfavorable metabolite ratio.

PubMed

Gardiner, Sharon J; Gearry, Richard B; Burt, Michael J; Chalmers-Watson, Teresa; Chapman, Bruce A; Ross, Alison G; Stedman, Catherine A M; Huelsen, Alexander; Barclay, Murray L

2011-01-01

Allopurinol potentiates azathioprine and 6-mercaptopurine (6-MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6-TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response. Sixteen individuals were identified who were taking azathioprine or 6-MP, and were commenced on allopurinol to improve a high 6-MMPN:TGN ratio. Metabolite concentrations were compared before and after commencing allopurinol, and markers of disease control were compared. The addition of 100-300 mg allopurinol daily and thiopurine dose reduction (17-50% of the original dose) resulted in a reduction of the median (and range) 6-MMPN concentration, from 11,643 (3,365-27,832) to 221 (55-844) pmol/8×10(8) red blood cells (RBC; P=0.0005), increased 6-TGN from 162 (125-300) to 332 (135-923) pmol/8×10(8) RBC (P=0.0005), and reduced the 6-MMPN:6-TGN ratio from 63 (12-199) to 1 (0.1-4.5) (P=0.0005). There was a significant reduction in steroid dose requirements at 12 months (P=0.04) and trends for improvement in other markers of disease control. One patient developed red cell aplasia that resolved upon stopping azathioprine and allopurinol. In those with a high 6-MMPN:6-TGN ratio (>20), response to thiopurine treatment might be improved by the addition of allopurinol, together with a reduced thiopurine dose and close hematological monitoring. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Intra-patient comparison of reduced-dose model-based iterative reconstruction with standard-dose adaptive statistical iterative reconstruction in the CT diagnosis and follow-up of urolithiasis.

PubMed

Tenant, Sean; Pang, Chun Lap; Dissanayake, Prageeth; Vardhanabhuti, Varut; Stuckey, Colin; Gutteridge, Catherine; Hyde, Christopher; Roobottom, Carl

2017-10-01

To evaluate the accuracy of reduced-dose CT scans reconstructed using a new generation of model-based iterative reconstruction (MBIR) in the imaging of urinary tract stone disease, compared with a standard-dose CT using 30% adaptive statistical iterative reconstruction. This single-institution prospective study recruited 125 patients presenting either with acute renal colic or for follow-up of known urinary tract stones. They underwent two immediately consecutive scans, one at standard dose settings and one at the lowest dose (highest noise index) the scanner would allow. The reduced-dose scans were reconstructed using both ASIR 30% and MBIR algorithms and reviewed independently by two radiologists. Objective and subjective image quality measures as well as diagnostic data were obtained. The reduced-dose MBIR scan was 100% concordant with the reference standard for the assessment of ureteric stones. It was extremely accurate at identifying calculi of 3 mm and above. The algorithm allowed a dose reduction of 58% without any loss of scan quality. A reduced-dose CT scan using MBIR is accurate in acute imaging for renal colic symptoms and for urolithiasis follow-up and allows a significant reduction in dose. • MBIR allows reduced CT dose with similar diagnostic accuracy • MBIR outperforms ASIR when used for the reconstruction of reduced-dose scans • MBIR can be used to accurately assess stones 3 mm and above.

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

Podonsky, Glenn S.

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protectionmore » of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.« less

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PubMed

Bonekamp, David; Wolf, M B; Roethke, M C; Pahernik, S; Hadaschik, B A; Hatiboglu, G; Kuru, T H; Popeneciu, I V; Chin, J L; Billia, M; Relle, J; Hafron, J; Nandalur, K R; Staruch, R M; Burtnyk, M; Hohenfellner, M; Schlemmer, H-P

2018-06-25

To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

Pyrrolidine-Acridine hybrid in Artemisinin-based combination: a pharmacodynamic study.

PubMed

Pandey, Swaroop Kumar; Biswas, Subhasish; Gunjan, Sarika; Chauhan, Bhavana Singh; Singh, Sunil Kumar; Srivastava, Kumkum; Singh, Sarika; Batra, Sanjay; Tripathi, Renu

2016-09-01

Aiming to develop new artemisinin-based combination therapy (ACT) for malaria, antimalarial effect of a new series of pyrrolidine-acridine hybrid in combination with artemisinin derivatives was investigated. Synthesis, antimalarial and cytotoxic evaluation of a series of hybrid of 2-(3-(substitutedbenzyl)pyrrolidin-1-yl)alkanamines and acridine were performed and mode of action of the lead compound was investigated. In vivo pharmacodynamic properties (parasite clearance time, parasite reduction ratio, dose and regimen determination) against multidrug resistant (MDR) rodent malaria parasite and toxicological parameters (median lethal dose, liver function test, kidney function test) were also investigated. 6-Chloro-N-(4-(3-(3,4-dimethoxybenzyl)pyrrolidin-1-yl)butyl)-2-methoxyacridin-9-amine (15c) has shown a dose dependent haem bio-mineralization inhibition and was found to be the most effective and safe compound against MDR malaria parasite in Swiss mice model. It displayed best antimalarial potential with artemether (AM) in vitro as well as in vivo. The combination also showed favourable pharmacodynamic properties and therapeutic response in mice with established MDR malaria infection and all mice were cured at the determined doses. The combination did not show toxicity at the doses administered to the Swiss mice. Taken together, our findings suggest that compound 15c is a potential partner with AM for the ACT and could be explored for further development.

Developmental neurotoxic effects of a low dose of TCE on a 3-D neurosphere system.

PubMed

Abdraboh, M E; Abdeen, S H; Salama, M; El-Husseiny, M; El-Sherbini, Y M; Eldeen, N M

2018-02-01

Trichloroethylene (TCE) is one of the industrial toxic byproducts that now persist in the air, soil, and water. Several studies have already illustrated the toxic effect of high doses of TCE on the biological functions of several organs. This study aims to highlight the toxic impact of a low dose of TCE (1 μmol/L) on the development of rat neural stem cells (NSCs). The subventricular zones (SVZ) of rat pup's brains were collected and minced, and the harvested cells were cultured in the presence of neural growth factors B27/N2 to develop neurospheres. The cells were then exposed to a dose of 1 μmol/L TCE for 1 or 2 weeks. The outcomes indicated a remarkable inhibitory effect of TCE on the differentiation capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect of TCE exposure. PCR results revealed a TCE-mediated suppression of the expression of the antioxidant enzyme SOD1. This paper illustrates, for the first time, a detailed examination of the toxic effects of an environmentally low dose of TCE on NCSs at the transcriptional, translational, and functional levels.

Treating primary dysmenorrhoea with acupuncture: a narrative review of the relationship between acupuncture 'dose' and menstrual pain outcomes.

PubMed

Armour, Mike; Smith, Caroline A

2016-12-01

A number of randomised controlled trials have been performed to determine the effectiveness or efficacy of acupuncture in primary dysmenorrhoea. The objective of this review was to explore the relationship between the 'dose' of the acupuncture intervention and menstrual pain outcomes. Eight databases were systematically searched for trials examining penetrating body acupuncture for primary dysmenorrhoea published in English up to September 2015. Dose components for each trial were extracted, assessed by the two authors and categorised by neurophysiological dose (number of needles, retention time and mode of stimulation), cumulative dose (total number and frequency of treatments), needle location and treatment timing. Eleven trials were included. Components of acupuncture dose were well reported across all trials. The relationship between needle location and menstrual pain demonstrated conflicting results. Treatment before the menses appeared to produce greater reductions in pain than treatment starting at the onset of menses. A single needle during menses may provide greater pain reduction compared to multiple needles. Conversely, multiple needles before menses were superior to a single needle. Electroacupuncture may provide more rapid pain reduction compared to manual acupuncture but may not have a significantly different effect on overall menstrual pain. There appear to be relationships between treatment timing and mode of needle stimulation, and menstrual pain outcomes. Needle location, number of needles used and frequency of treatment show clear dose-response relationships with menstrual pain outcomes. Current research is insufficient to make definitive clinical recommendations regarding optimum dose parameters for treating primary dysmenorrhoea. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The impact of various protective tools on the dose reduction in the eye lens in an interventional cardiology-clinical study.

PubMed

Domienik, J; Bissinger, A; Grabowicz, W; Jankowski, Ł; Kręcki, R; Makowski, M; Masiarek, K; Plewka, M; Lubiński, A; Peruga, J Z

2016-06-01

The aim of the study was to check, in clinical practice, the potential for the dose reduction of lead eyewear and a ceiling-suspended shield used to protect the eye lens of physicians working in interventional cardiology. To this end, for the lead eyewear, the dose reduction factors were derived to correct the readings from a dosimeter used routinely outside the glasses. Four types of lead eyewear with attached loose thermoluminescent dosimeters and EYE-D dosimeters were worn by physicians in two clinical centres, for two-month periods, during coronary angiography (CA), percutaneous coronary intervention (PCI), and pacemaker procedures. In order to analyse, separately, how a ceiling-suspended lead screen absorbs the scattered radiation, a series of measurements was carried out during single CA/PCI procedures performed with and without the protection. The lead eyewear may reduce the doses to the eye closest to the x-ray tube by a factor between 1.1 and 3.4, depending on its model and the physician's position. The effectiveness of the eyewear may, however, vary-even for the same model and physician-almost twofold between different working periods. The ceiling-suspended shield decreases the doses in clinical practice by a factor of 2.3. The annual eye lens doses without the eyewear estimated from routine measurements are high-above or close to the new eye lens dose limit established by the recent EU Basic Safety Standards, even though the ceiling-suspended shield was used. Therefore, to comply with the new dose limit that is set in the Directive, protection of the eyes of physicians with high workloads might require the use of both the eyewear and the ceiling-suspended shield.

Reviewing long-term antidepressants can reduce drug burden: a prospective observational cohort study

PubMed Central

Johnson, Chris F; Macdonald, Hector J; Atkinson, Pauline; Buchanan, Alasdair I; Downes, Noreen; Dougall, Nadine

2012-01-01

Background Antidepressant prescribing continues to rise. Contributing factors are increased long-term prescribing and possibly the use of higher selective serotonin re-uptake inhibitor (SSRI) doses. Aim To review general practice patients prescribed the same antidepressant long-term (≥2 years) and evaluate prescribing and management pre and post-review. Design and setting Prospective observational cohort study using routine data from 78 urban general practices, Scotland. Method All patients prescribed antidepressants (excluding amitriptyline) for ≥2 years were identified from records November 2009 to March 2010. GPs selected patients for face-to-face review of clinical condition and medication, December 2009 to September 2010. Pre- and post-review data were collected; average antidepressant doses and changes in prescribed daily doses were calculated. Onward referral to support services was recorded. Results 8.6% (33 312/388 656) of all registered patients were prescribed an antidepressant, 47.1% (15 689) were defined as long-term users and 2849 (18.2%) were reviewed. 811 (28.5%) patients reviewed had a change in antidepressant therapy: 7.0% stopped, 12.8% reduced dose, 5.3% increased dose, and 3.4% changed antidepressant, resulting in 9.5% (95% CI = 9.1% to 9.8% P<0.001) reduction in prescribed daily dose and 8.1% reduction in prescribing costs. 6.3% were referred onwards, half to NHS Mental Health Services. Pre-review SSRI doses were 10–30% higher than previously reported. Conclusion Almost half of all people prescribed antidepressants were long-term users. Appropriate reductions in prescribing can be achieved by reviewing patients. Higher SSRI doses may be contributing to current antidepressant growth. PMID:23211181

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

PubMed

Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

2015-07-01

To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

PubMed

Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

2016-03-23

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

Low-dose CT imaging of a total hip arthroplasty phantom using model-based iterative reconstruction and orthopedic metal artifact reduction.

PubMed

Wellenberg, R H H; Boomsma, M F; van Osch, J A C; Vlassenbroek, A; Milles, J; Edens, M A; Streekstra, G J; Slump, C H; Maas, M

2017-05-01

To compare quantitative measures of image quality, in terms of CT number accuracy, noise, signal-to-noise-ratios (SNRs), and contrast-to-noise ratios (CNRs), at different dose levels with filtered-back-projection (FBP), iterative reconstruction (IR), and model-based iterative reconstruction (MBIR) alone and in combination with orthopedic metal artifact reduction (O-MAR) in a total hip arthroplasty (THA) phantom. Scans were acquired from high- to low-dose (CTDI vol : 40.0, 32.0, 24.0, 16.0, 8.0, and 4.0 mGy) at 120- and 140- kVp. Images were reconstructed using FBP, IR (iDose 4 level 2, 4, and 6) and MBIR (IMR, level 1, 2, and 3) with and without O-MAR. CT number accuracy in Hounsfield Units (HU), noise or standard deviation, SNRs, and CNRs were analyzed. The IMR technique showed lower noise levels (p < 0.01), higher SNRs (p < 0.001) and CNRs (p < 0.001) compared with FBP and iDose 4 in all acquisitions from high- to low-dose with constant CT numbers. O-MAR reduced noise (p < 0.01) and improved SNRs (p < 0.01) and CNRs (p < 0.001) while improving CT number accuracy only at a low dose. At the low dose of 4.0 mGy, IMR level 1, 2, and 3 showed 83%, 89%, and 95% lower noise values, a factor 6.0, 9.2, and 17.9 higher SNRs, and 5.7, 8.8, and 18.2 higher CNRs compared with FBP respectively. Based on quantitative analysis of CT number accuracy, noise values, SNRs, and CNRs, we conclude that the combined use of IMR and O-MAR enables a reduction in radiation dose of 83% compared with FBP and iDose 4 in the CT imaging of a THA phantom.

Radiation dose in 320-slice multidetector cardiac CT: a single center experience of evolving dose minimization.

PubMed

Tung, Matthew K; Cameron, James D; Casan, Joshua M; Crossett, Marcus; Troupis, John M; Meredith, Ian T; Seneviratne, Sujith K

2013-01-01

Minimization of radiation exposure remains an important subject that occurs in parallel with advances in scanner technology. We report our experience of evolving radiation dose and its determinants after the introduction of 320-multidetector row cardiac CT within a single tertiary cardiology referral service. Four cohorts of consecutive patients (total 525 scans), who underwent cardiac CT at defined time points as early as 2008, are described. These include a cohort just after scanner installation, after 2 upgrades of the operating system, and after introduction of an adaptive iterative image reconstruction algorithm. The proportions of nondiagnostic coronary artery segments and studies with nondiagnostic segments were compared between cohorts. Significant reductions were observed in median radiation doses in all cohorts compared with the initial cohort (P < .001). Median dose-length product fell from 944 mGy · cm (interquartile range [IQR], 567.3-1426.5 mGy · cm) to 156 mGy · cm (IQR, 99.2-265.0 mGy · cm). Although the proportion of prospectively triggered scans has increased, reductions in radiation dose have occurred independently of distribution of scan formats. In multiple regression that combined all groups, determinants of dose-length product were tube output, the number of cardiac cycles scanned, tube voltage, scan length, scan format, body mass index, phase width, and heart rate (adjusted R(2) = 0.85, P < .001). The proportion of nondiagnostic coronary artery segments was slightly increased in group 4 (2.9%; P < .01). While maintaining diagnostic quality in 320-multidetector row cardiac CT, the radiation dose has decreased substantially because of a combination of dose-reduction protocols and technical improvements. Continued minimization of radiation dose will increase the potential for cardiac CT to expand as a cardiac imaging modality. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

CT image electron density quantification in regions with metal implants: implications for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Jechel, Christopher Alexander

In radiotherapy planning, computed tomography (CT) images are used to quantify the electron density of tissues and provide spatial anatomical information. Treatment planning systems use these data to calculate the expected spatial distribution of absorbed dose in a patient. CT imaging is complicated by the presence of metal implants which cause increased image noise, produce artifacts throughout the image and can exceed the available range of CT number values within the implant, perturbing electron density estimates in the image. Furthermore, current dose calculation algorithms do not accurately model radiation transport at metal-tissue interfaces. Combined, these issues adversely affect the accuracy of dose calculations in the vicinity of metal implants. As the number of patients with orthopedic and dental implants grows, so does the need to deliver safe and effective radiotherapy treatments in the presence of implants. The Medical Physics group at the Cancer Centre of Southeastern Ontario and Queen's University has developed a Cobalt-60 CT system that is relatively insensitive to metal artifacts due to the high energy, nearly monoenergetic Cobalt-60 photon beam. Kilovoltage CT (kVCT) images, including images corrected using a commercial metal artifact reduction tool, were compared to Cobalt-60 CT images throughout the treatment planning process, from initial imaging through to dose calculation. An effective metal artifact reduction algorithm was also implemented for the Cobalt-60 CT system. Electron density maps derived from the same kVCT and Cobalt-60 CT images indicated the impact of image artifacts on estimates of photon attenuation for treatment planning applications. Measurements showed that truncation of CT number data in kVCT images produced significant mischaracterization of the electron density of metals. Dose measurements downstream of metal inserts in a water phantom were compared to dose data calculated using CT images from kVCT and Cobalt-60 systems with and without artifact correction. The superior accuracy of electron density data derived from Cobalt-60 images compared to kVCT images produced calculated dose with far better agreement with measured results. These results indicated that dose calculation errors from metal image artifacts are primarily due to misrepresentation of electron density within metals rather than artifacts surrounding the implants.

Development of an applicator for eye lens dosimetry during radiotherapy.

PubMed

Park, J M; Lee, J; Kim, H S; Ye, S-J; Kim, J-I

2014-10-01

To develop an applicator for in vivo measurements of lens dose during radiotherapy. A contact lens-shaped applicator made of acrylic was developed for in vivo measurements of lens dose. This lens applicator allows the insertion of commercially available metal oxide semiconductor field effect transistors (MOSFETs) dosemeters. CT images of an anthropomorphic phantom with and without the applicator were acquired. Ten volumetric modulated arc therapy plans each for the brain and the head and neck cancer were generated and delivered to an anthropomorphic phantom. The differences between the measured and the calculated doses at the lens applicator, as well as the differences between the measured and the calculated doses at the surface of the eyelid were acquired. The average difference between the measured and the calculated doses with the applicator was 3.1 ± 1.8 cGy with a micro MOSFET and 2.8 ± 1.3 cGy with a standard MOSFET. The average difference without the lens applicator was 4.8 ± 5.2 cGy with the micro MOSFET and 5.7 ± 6.5 cGy with the standard MOSFET. The maximum difference with the micro MOSFET was 10.5 cGy with the applicator and 21.1 cGy without the applicator. For the standard MOSFET, it was 6.8 cGy with the applicator and 27.6 cGy without the applicator. The lens applicator allowed reduction of the differences between the calculated and the measured doses during in vivo measurement for the lens compared with in vivo measurement at the surface of the eyelid. By using an applicator for in vivo dosimetry of the eye lens, it was possible to reduce the measurement uncertainty.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

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

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

Developing the radiation protection safety culture in the UK.

PubMed

Cole, P; Hallard, R; Broughton, J; Coates, R; Croft, J; Davies, K; Devine, I; Lewis, C; Marsden, P; Marsh, A; McGeary, R; Riley, P; Rogers, A; Rycraft, H; Shaw, A

2014-06-01

In the UK, as elsewhere, there is potential to improve how radiological challenges are addressed through improvement in, or development of, a strong radiation protection (RP) safety culture. In preliminary work in the UK, two areas have been identified as having a strong influence on UK society: the healthcare and nuclear industry sectors. Each has specific challenges, but with many overlapping common factors. Other sectors will benefit from further consideration.In order to make meaningful comparisons between these two principal sectors, this paper is primarily concerned with cultural aspects of RP in the working environment and occupational exposures rather than patient doses.The healthcare sector delivers a large collective dose to patients each year, particularly for diagnostic purposes, which continues to increase. Although patient dose is not the focus, it must be recognised that collective patient dose is inevitably linked to collective occupational exposure, especially in interventional procedures.The nuclear industry faces major challenges as work moves from operations to decommissioning on many sites. This involves restarting work in the plants responsible for the much higher radiation doses of the 1960/70s, but also performing tasks that are considerably more difficult and hazardous than those original performed in these plants.Factors which influence RP safety culture in the workplace are examined, and proposals are considered for a series of actions that may lead to an improvement in RP culture with an associated reduction in dose in many work areas. These actions include methods to improve knowledge and awareness of radiation safety, plus ways to influence management and colleagues in the workplace. The exchange of knowledge about safety culture between the nuclear industry and medical areas may act to develop RP culture in both sectors, and have a wider impact in other sectors where exposures to ionising radiations can occur.

Post onset, oral rapamycin treatment delays development of mitochondrial encephalopathy only at supramaximal doses.

PubMed

Felici, Roberta; Buonvicino, Daniela; Muzzi, Mirko; Cavone, Leonardo; Guasti, Daniele; Lapucci, Andrea; Pratesi, Sara; De Cesaris, Francesco; Luceri, Francesca; Chiarugi, Alberto

2017-05-01

Mitochondrial encephalopathies are fatal, infantile neurodegenerative disorders caused by a deficit of mitochondrial functioning, for which there is urgent need to identify efficacious pharmacological treatments. Recent evidence shows that rapamycin administered both intraperitoneally or in the diet delays disease onset and enhances survival in the Ndufs4 null mouse model of mitochondrial encephalopathy. To delineate the clinical translatability of rapamycin in treatment of mitochondrial encephalopathy, we evaluated the drug's effects on disease evolution and mitochondrial parameters adopting treatment paradigms with fixed daily, oral doses starting at symptom onset in Ndufs4 knockout mice. Molecular mechanisms responsible for the pharmacodynamic effects of rapamycin were also evaluated. We found that rapamycin did not affect disease development at clinically-relevant doses (0.5 mg kg -1 ). Conversely, an oral dose previously adopted for intraperitoneal administration (8 mg kg -1 ) delayed development of neurological symptoms and increased median survival by 25%. Neurological improvement and lifespan were not further increased when the dose raised to 20 mg kg -1 . Notably, rapamycin at 8 mg kg -1 did not affect the reduced expression of respiratory complex subunits, as well as mitochondrial number and mtDNA content. This treatment regimen however significantly ameliorated architecture of mitochondria cristae in motor cortex and cerebellum. However, reduction of mTOR activity by rapamycin was not consistently found within the brain of knockout mice. Overall, data show the ability of rapamycin to improve ultrastructure of dysfunctional mitochondria and corroborate its therapeutic potential in mitochondrial disorders. The non-clinical standard doses required, however, raise concerns about its rapid and safe clinical transferability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cargo and Container X-Ray Inspection with Intra-Pulse Multi-Energy Method for Material Discrimination

NASA Astrophysics Data System (ADS)

Saverskiy, Aleksandr Y.; Dinca, Dan-Cristian; Rommel, J. Martin

The Intra-Pulse Multi-Energy (IPME) method of material discrimination mitigates main disadvantages of the traditional "interlaced" approach: ambiguity caused by sampling different regions of cargo and reduction of effective scanning speed. A novel concept of creating multi-energy probing pulses using a standing-wave structure allows maintaining a constant energy spectrum while changing the time duration of each sub-pulse and thus enables adaptive cargo inspection. Depending on the cargo density, the dose delivered to the inspected object is optimized for best material discrimination, maximum material penetration, or lowest dose to cargo. A model based on Monte-Carlo simulation and experimental reference points were developed for the optimization of inspection conditions.

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

Caillet, V; Colvill, E; Royal North Shore Hospital, Sydney, NSW

Purpose: The objective of this study was to investigate the dosimetric benefits of multi-leaf collimator (MLC) tracking for lung SABR treatments in end-to-end clinically realistic planning and delivery scenarios. Methods: The clinical benefits of MLC tracking were assessed using previously delivered treatment plans and physical experiments. The 10 most recent single lesion lung SABR patients were re-planned following a 4D-GTV-based real-time adaptive protocol (PTV defined as the end-of-exhalation GTV plus 5.0 mm margins). The plans were delivered on a Trilogy Varian linac. Electromagnetic transponders (Calypso, Varian Medical Systems, USA) were embedded into a programmable moving phantom (HexaMotion platform) tracked withmore » the Varian Calypso system. For each physical experiment, the MLC positions were collected and used as input for dose reconstruction. For both planned and physical experiments, the OAR dose metrics from the conventional and real-time adaptive SABR plans (Mean Lung Dose (MLD), V20 for lung, and near-maximum dose (D2%) for spine and heart) were statistically compared. The Wilcoxon test was used to compare plan and physical experiment dose metrics. Results: While maintaining target coverage, percentage reductions in dose metrics to the OARs were observed for both planned and physical experiments. Comparing the two plans showed MLD percentage reduction (MLDr) of 25.4% (absolute differences of 1.41 Gy) and 28.9% (1.29%) for the V20r. D2% percentage reduction for spine and heart were respectively 27.9% (0.3 Gy) and 20.2% (0.3 Gy). For the physical experiments, MLDr was 23.9% (1.3 Gy), and V20r 37.4% (1.6%). D2% reduction for spine and heart were respectively 27.3% (0.3 Gy) and 19.6% (0.3 Gy). For both plans and physical experiments, significant OAR dose differences (p<0.05) were found between the conventional SABR and real-time adaptive plans. Conclusion: Application of MLC tracking for lung SABR patients has the potential to reduce the dose to OARs during radiation therapy.« less

Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

PubMed

Pozzi, Marco; Pisano, Simone; Bertella, Silvana; Capuano, Annalisa; Rizzo, Renata; Antoniazzi, Stefania; Auricchio, Fabiana; Carnovale, Carla; Cattaneo, Dario; Ferrajolo, Carmen; Gentili, Marta; Guastella, Giuseppe; Mani, Elisa; Rafaniello, Concetta; Riccio, Maria Pia; Scuderi, Maria Grazia; Sperandeo, Serena; Sportiello, Liberata; Villa, Laura; Radice, Sonia; Clementi, Emilio; Rossi, Francesco; Pascotto, Antonio; Bernardini, Renato; Molteni, Massimo; Bravaccio, Carmela

2016-12-01

The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting. © Copyright 2016 Physicians Postgraduate Press, Inc.