Science.gov

Sample records for low-dose ct head-to-head

  1. [Indications for low-dose CT in the emergency setting].

    PubMed

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  2. Adaptively Tuned Iterative Low Dose CT Image Denoising.

    PubMed

    Hashemi, SayedMasoud; Paul, Narinder S; Beheshti, Soosan; Cobbold, Richard S C

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

  3. Adaptively Tuned Iterative Low Dose CT Image Denoising

    PubMed Central

    Hashemi, SayedMasoud; Paul, Narinder S.; Beheshti, Soosan; Cobbold, Richard S. C.

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

  4. Segmentation of individual ribs from low-dose chest CT

    NASA Astrophysics Data System (ADS)

    Lee, Jaesung; Reeves, Anthony P.

    2010-03-01

    Segmentation of individual ribs and other bone structures in chest CT images is important for anatomical analysis, as the segmented ribs may be used as a baseline reference for locating organs within a chest as well as for identification and measurement of any geometric abnormalities in the bone. In this paper we present a fully automated algorithm to segment the individual ribs from low-dose chest CT scans. The proposed algorithm consists of four main stages. First, all the high-intensity bone structure present in the scan is segmented. Second, the centerline of the spinal canal is identified using a distance transform of the bone segmentation. Then, the seed region for every rib is detected based on the identified centerline, and each rib is grown from the seed region and separated from the corresponding vertebra. This algorithm was evaluated using 115 low-dose chest CT scans from public databases with various slice thicknesses. The algorithm parameters were determined using 5 scans, and remaining 110 scans were used to evaluate the performance of the segmentation algorithm. The outcome of the algorithm was inspected by an author for the correctness of the segmentation. The results indicate that over 98% of the individual ribs were correctly segmented with the proposed algorithm.

  5. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  6. Myocardial CT Perfusion Imaging and SPECT for the Diagnosis of Coronary Artery Disease: A Head-to-Head Comparison from the CORE320 Multicenter Diagnostic Performance Study

    PubMed Central

    Mehra, Vishal C.; Chen, Marcus Y.; Kitagawa, Kakuya; Arbab-Zadeh, Armin; Miller, Julie M.; Matheson, Matthew B.; Vavere, Andrea L.; Kofoed, Klaus F.; Rochitte, Carlos E.; Dewey, Marc; Yaw, Tan S.; Niinuma, Hiroyuki; Brenner, Winfried; Cox, Christopher; Clouse, Melvin E.; Lima, João A. C.; Di Carli, Marcelo

    2014-01-01

    Purpose To compare the diagnostic performance of myocardial computed tomographic (CT) perfusion imaging and single photon emission computed tomography (SPECT) perfusion imaging in the diagnosis of anatomically significant coronary artery disease (CAD) as depicted at invasive coronary angiography. Materials and Methods This study was approved by the institutional review board. Written informed consent was obtained from all patients. Sixteen centers enrolled 381 patients from November 2009 to July 2011. Patients underwent rest and adenosine stress CT perfusion imaging and rest and either exercise or pharmacologic stress SPECT before and within 60 days of coronary angiography. Images from CT perfusion imaging, SPECT, and coronary angiography were interpreted at blinded, independent core laboratories. The primary diagnostic parameter was the area under the receiver operating characteristic curve (Az). Sensitivity and specificity were calculated with use of prespecified cutoffs. The reference standard was a stenosis of at least 50% at coronary angiography as determined with quantitative methods. Results CAD was diagnosed in 229 of the 381 patients (60%). The per-patient sensitivity and specificity for the diagnosis of CAD (stenosis ≥50%) were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95% confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion imaging for single- and multivessel CAD was higher than that of SPECT, with sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT. Conclusion The overall performance of myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis ≥50%), as demonstrated with the

  7. Algorithm-enabled low-dose micro-CT imaging.

    PubMed

    Han, Xiao; Bian, Junguo; Eaker, Diane R; Kline, Timothy L; Sidky, Emil Y; Ritman, Erik L; Pan, Xiaochuan

    2011-03-01

    Micro-computed tomography (micro-CT) is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300-1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging.

  8. Ultra Low Dose CT Pulmonary Angiography with Iterative Reconstruction

    PubMed Central

    Koehler, Thomas; Fingerle, Alexander A.; Brendel, Bernhard; Richter, Vivien; Rasper, Michael; Rummeny, Ernst J.; Noël, Peter B.; Münzel, Daniela

    2016-01-01

    Objective Evaluation of a new iterative reconstruction algorithm (IMR) for detection/rule-out of pulmonary embolism (PE) in ultra-low dose computed tomography pulmonary angiography (CTPA). Methods Lower dose CT data sets were simulated based on CTPA examinations of 16 patients with pulmonary embolism (PE) with dose levels (DL) of 50%, 25%, 12.5%, 6.3% or 3.1% of the original tube current setting. Original CT data sets and simulated low-dose data sets were reconstructed with three reconstruction algorithms: the standard reconstruction algorithm “filtered back projection” (FBP), the first generation iterative reconstruction algorithm iDose and the next generation iterative reconstruction algorithm “Iterative Model Reconstruction” (IMR). In total, 288 CTPA data sets (16 patients, 6 tube current levels, 3 different algorithms) were evaluated by two blinded radiologists regarding image quality, diagnostic confidence, detectability of PE and contrast-to-noise ratio (CNR). Results iDose and IMR showed better detectability of PE than FBP. With IMR, sensitivity for detection of PE was 100% down to a dose level of 12.5%. iDose and IMR showed superiority to FBP regarding all characteristics of subjective (diagnostic confidence in detection of PE, image quality, image noise, artefacts) and objective image quality. The minimum DL providing acceptable diagnostic performance was 12.5% (= 0.45 mSv) for IMR, 25% (= 0.89 mSv) for iDose and 100% (= 3.57 mSv) for FBP. CNR was significantly (p < 0.001) improved by IMR compared to FBP and iDose at all dose levels. Conclusion By using IMR for detection of PE, dose reduction for CTPA of up to 75% is possible while maintaining full diagnostic confidence. This would result in a mean effective dose of approximately 0.9 mSv for CTPA. PMID:27611830

  9. Personalized low dose CT via variable kVp

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Jin, Yannan; Yao, Yangyang; Wu, Mingye; Yan, Ming; Tao, Kun; Yin, Zhye; De Man, Bruno

    2015-03-01

    Computerized Tomography (CT) is a powerful radiographic imaging technology but the health risk due to the exposure of x-ray radiation has drawn wide concern. In this study, we propose to use kVp modulation to reduce the radiation dose and achieve the personalized low dose CT. Two sets of simulation are performed to demonstrate the effectiveness of kVp modulation and the corresponding calibration. The first simulation used the helical body phantom (HBP) that is an elliptical water cylinder with high density bone inserts. The second simulation uses the NCAT phantom to emulate the practical use of kVp modulation approach with region of interest (ROI) selected in the cardiac region. The kVp modulation profile could be optimized view by view based on the knowledge of patient attenuation. A second order correction is applied to eliminate the beam hardening artifacts. To simplify the calibration process, we first generate the calibration vectors for a few representative spectra and then acquire other calibration vectors with interpolation. The simulation results demonstrate the beam hardening artifacts in the images with kVp modulation can be eliminated with proper beam hardening correction. The results also show that the simplification of calibration did not impair the image quality: the calibration with the simplified and the complete vectors both eliminate the artifacts effectively and the results are comparable. In summary, this study demonstrates the feasibility of kVp modulation and gives a practical way to calibrate the high order beam hardening artifacts.

  10. Ultra-low dose CT attenuation correction for PET/CT.

    PubMed

    Xia, Ting; Alessio, Adam M; De Man, Bruno; Manjeshwar, Ravindra; Asma, Evren; Kinahan, Paul E

    2012-01-21

    A challenge for positron emission tomography/computed tomography (PET/CT) quantitation is patient respiratory motion, which can cause an underestimation of lesion activity uptake and an overestimation of lesion volume. Several respiratory motion correction methods benefit from longer duration CT scans that are phase matched with PET scans. However, even with the currently available, lowest dose CT techniques, extended duration cine CT scans impart a substantially high radiation dose. This study evaluates methods designed to reduce CT radiation dose in PET/CT scanning. We investigated selected combinations of dose reduced acquisition and noise suppression methods that take advantage of the reduced requirement of CT for PET attenuation correction (AC). These include reducing CT tube current, optimizing CT tube voltage, adding filtration, CT sinogram smoothing and clipping. We explored the impact of these methods on PET quantitation via simulations on different digital phantoms. CT tube current can be reduced much lower for AC than that in low dose CT protocols. Spectra that are higher energy and narrower are generally more dose efficient with respect to PET image quality. Sinogram smoothing could be used to compensate for the increased noise and artifacts at radiation dose reduced CT images, which allows for a further reduction of CT dose with no penalty for PET image quantitation. When CT is not used for diagnostic and anatomical localization purposes, we showed that ultra-low dose CT for PET/CT is feasible. The significant dose reduction strategies proposed here could enable respiratory motion compensation methods that require extended duration CT scans and reduce radiation exposure in general for all PET/CT imaging. PMID:22156174

  11. Ultra-low dose CT attenuation correction for PET/CT

    NASA Astrophysics Data System (ADS)

    Xia, Ting; Alessio, Adam M.; De Man, Bruno; Manjeshwar, Ravindra; Asma, Evren; Kinahan, Paul E.

    2012-01-01

    A challenge for positron emission tomography/computed tomography (PET/CT) quantitation is patient respiratory motion, which can cause an underestimation of lesion activity uptake and an overestimation of lesion volume. Several respiratory motion correction methods benefit from longer duration CT scans that are phase matched with PET scans. However, even with the currently available, lowest dose CT techniques, extended duration cine CT scans impart a substantially high radiation dose. This study evaluates methods designed to reduce CT radiation dose in PET/CT scanning. We investigated selected combinations of dose reduced acquisition and noise suppression methods that take advantage of the reduced requirement of CT for PET attenuation correction (AC). These include reducing CT tube current, optimizing CT tube voltage, adding filtration, CT sinogram smoothing and clipping. We explored the impact of these methods on PET quantitation via simulations on different digital phantoms. CT tube current can be reduced much lower for AC than that in low dose CT protocols. Spectra that are higher energy and narrower are generally more dose efficient with respect to PET image quality. Sinogram smoothing could be used to compensate for the increased noise and artifacts at radiation dose reduced CT images, which allows for a further reduction of CT dose with no penalty for PET image quantitation. When CT is not used for diagnostic and anatomical localization purposes, we showed that ultra-low dose CT for PET/CT is feasible. The significant dose reduction strategies proposed here could enable respiratory motion compensation methods that require extended duration CT scans and reduce radiation exposure in general for all PET/CT imaging.

  12. Limits of Ultra-Low Dose CT Attenuation Correction for PET/CT.

    PubMed

    Xia, Ting; Alessio, Adam M; Kinahan, Paul E

    2010-01-29

    We present an analysis of the effects of ultra-low dose X-ray computerized tomography (CT) based attenuation correction for positron emission tomography (PET). By ultra low dose we mean less than approximately 5 mAs or 0.5 mSv total effective whole body dose. The motivation is the increased interest in using respiratory motion information acquired during the CT scan for both phase-matched CT-based attenuation correction and for motion estimation. Since longer duration CT scans are desired, radiation dose to the patient can be a limiting factor. In this study we evaluate the impact of reducing photon flux rates in the CT data on the reconstructed PET image by using the CATSIM simulation tool for the CT component and the ASIM simulation tool for the PET component. The CT simulation includes effects of the x-ray tube spectra, beam conditioning, bowtie filter, detector noise, and bean hardening correction. The PET simulation includes the effect of attenuation and photon counting. Noise and bias in the PET image were evaluated from multiple realizations of test objects. We show that techniques can be used to significantly reduce the mAs needed for CT based attenuation correction if the CT is not used for diagnostic purposes. The limiting factor, however, is not the noise in the CT image but rather the bias introduced by CT sinogram elements with no detected flux. These results constrain the methods that can be used to lower CT dose in a manner suitable for attenuation correction of PET data. We conclude that ultra-low-dose CT for attenuation correction of PET data is feasible with current PET/CT scanners.

  13. A Simple Low-dose X-ray CT Simulation from High-dose Scan

    PubMed Central

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong

    2015-01-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID:26543245

  14. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  15. Low-dose high-resolution CT of lung parenchyma

    SciTech Connect

    Zwirewich, C.V.; Mayo, J.R.; Mueller, N.L. )

    1991-08-01

    To evaluate the efficacy of low-dose high-resolution computed tomography (HRCT) in the assessment of lung parenchyma, three observers reviewed the scans of 31 patients. The 1.5-mm-collimation, 2-second, 120-kVp scans were obtained at 20 and 200 mA at selected identical levels in the chest. The observers evaluated the visualization of normal pulmonary anatomy, various parenchymal abnormalities and their distribution, and artifacts. The low-dose and conventional scans were equivalent in the evaluation of vessels, lobar and segmental bronchi, and anatomy of secondary pulmonary lobules, and in characterizing the extent and distribution of reticulation, honeycomb cysts, and thickened interlobular septa. The low-dose technique failed to demonstrate ground-glass opacity in two of 10 cases (20%) and emphysema in one of nine cases (11%), in which they were evident but subtle on the high-dose scans. These differences were not statistically significant. Linear streak artifact was more prominent on images acquired with the low-dose technique, but the two techniques were judged equally diagnostic in 97% of cases. The authors conclude that HRCT images acquired at 20 mA yield anatomic information equivalent to that obtained with 200-mA scans in the majority of patients, without significant loss of spatial resolution or image degradation due to linear streak artifact.

  16. 20 percent lower lung cancer mortality with low-dose CT vs chest X-ray

    Cancer.gov

    Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray.

  17. Attenuation correction of PET cardiac data with low-dose average CT in PET/CT

    SciTech Connect

    Pan Tinsu; Mawlawi, Osama; Luo, Dershan; Liu, Hui H.; Chi Paichun, M.; Mar, Martha V.; Gladish, Gregory; Truong, Mylene; Erasmus, Jeremy Jr.; Liao Zhongxing; Macapinlac, H. A.

    2006-10-15

    We proposed a low-dose average computer tomography (ACT) for attenuation correction (AC) of the PET cardiac data in PET/CT. The ACT was obtained from a cine CT scan of over one breath cycle per couch position while the patient was free breathing. We applied this technique on four patients who underwent tumor imaging with {sup 18}F-FDG in PET/CT, whose PET data showed high uptake of {sup 18}F-FDG in the heart and whose CT and PET data had misregistration. All four patients did not have known myocardiac infarction or ischemia. The patients were injected with 555-740 MBq of {sup 18}F-FDG and scanned 1 h after injection. The helical CT (HCT) data were acquired in 16 s for the coverage of 100 cm. The PET acquisition was 3 min per bed of 15 cm. The duration of cine CT acquisition per 2 cm was 5.9 s. We used a fast gantry rotation cycle time of 0.5 s to minimize motion induced reconstruction artifacts in the cine CT images, which were averaged to become the ACT images for AC of the PET data. The radiation dose was about 5 mGy for 5.9 s cine duration. The selection of 5.9 s was based on our analysis of the respiratory signals of 600 patients; 87% of the patients had average breath cycles of less than 6 s and 90% had standard deviations of less than 1 s in the period of breath cycle. In all four patient studies, registrations between the CT and the PET data were improved. An increase of average uptake in the anterior and the lateral walls up to 48% and a decrease of average uptake in the septal and the inferior walls up to 16% with ACT were observed. We also compared ACT and conventional slow scan CT (SSCT) of 4 s duration in one patient study and found ACT was better than SSCT in depicting average respiratory motion and the SSCT images showed motion-induced reconstruction artifacts. In conclusion, low-dose ACT improved registration of the CT and the PET data in the heart region in our study of four patients. ACT was superior than SSCT for depicting average respiration

  18. Spectrotemporal CT data acquisition and reconstruction at low dose

    PubMed Central

    Clark, Darin P.; Lee, Chang-Lung; Kirsch, David G.; Badea, Cristian T.

    2015-01-01

    Purpose: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D + dual energy + time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. Methods: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction

  19. Spectrotemporal CT data acquisition and reconstruction at low dose

    SciTech Connect

    Clark, Darin P.; Badea, Cristian T.; Lee, Chang-Lung; Kirsch, David G.

    2015-11-15

    Purpose: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D + dual energy + time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. Methods: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction

  20. Fast reconstruction of low dose proton CT by sinogram interpolation

    NASA Astrophysics Data System (ADS)

    Hansen, David C.; Sangild Sørensen, Thomas; Rit, Simon

    2016-08-01

    Proton computed tomography (CT) has been demonstrated as a promising image modality in particle therapy planning. It can reduce errors in particle range calculations and consequently improve dose calculations. Obtaining a high imaging resolution has traditionally required computationally expensive iterative reconstruction techniques to account for the multiple scattering of the protons. Recently, techniques for direct reconstruction have been developed, but these require a higher imaging dose than the iterative methods. No previous work has compared the image quality of the direct and the iterative methods. In this article, we extend the methodology for direct reconstruction to be applicable for low imaging doses and compare the obtained results with three state-of-the-art iterative algorithms. We find that the direct method yields comparable resolution and image quality to the iterative methods, even at 1 mSv dose levels, while yielding a twentyfold speedup in reconstruction time over previously published iterative algorithms.

  1. Automated coronary artery calcification detection on low-dose chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Cham, Matthew D.; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

    2014-03-01

    Coronary artery calcification (CAC) measurement from low-dose CT images can be used to assess the risk of coronary artery disease. A fully automatic algorithm to detect and measure CAC from low-dose non-contrast, non-ECG-gated chest CT scans is presented. Based on the automatically detected CAC, the Agatston score (AS), mass score and volume score were computed. These were compared with scores obtained manually from standard-dose ECG-gated scans and low-dose un-gated scans of the same patient. The automatic algorithm segments the heart region based on other pre-segmented organs to provide a coronary region mask. The mitral valve and aortic valve calcification is identified and excluded. All remaining voxels greater than 180HU within the mask region are considered as CAC candidates. The heart segmentation algorithm was evaluated on 400 non-contrast cases with both low-dose and regular dose CT scans. By visual inspection, 371 (92.8%) of the segmentations were acceptable. The automated CAC detection algorithm was evaluated on 41 low-dose non-contrast CT scans. Manual markings were performed on both low-dose and standard-dose scans for these cases. Using linear regression, the correlation of the automatic AS with the standard-dose manual scores was 0.86; with the low-dose manual scores the correlation was 0.91. Standard risk categories were also computed. The automated method risk category agreed with manual markings of gated scans for 24 cases while 15 cases were 1 category off. For low-dose scans, the automatic method agreed with 33 cases while 7 cases were 1 category off.

  2. SU-E-P-03: Implementing a Low Dose Lung Screening CT Program Meeting Regulatory Requirements

    SciTech Connect

    LaFrance, M; Marsh, S; O'Donnell, G

    2014-06-01

    Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Purpose: Provide guidance to the Radiology Departments with the intent of implementing a Low Dose CT Screening Program using different CT Scanners with multiple techniques within the framework of the required state regulations. Method: State Requirements for the purpose of implementing a Low Dose CT Lung Protocol required working with the Radiology and Pulmonary Department in setting up a Low Dose Screening Protocol designed to reduce the radiation burden to the patients enrolled. Radiation dose measurements (CTDIvol) for various CT manufacturers (Siemens16, Siemens 64, Philips 64, and Neusoft128) for three different weight based protocols. All scans were reviewed by the Radiologist. Prior to starting a low dose lung screening protocol, information had to be submitted to the state for approval. Performing a Healing Arts protocol requires extensive information. This not only includes name and address of the applicant but a detailed description of the disease, the x-ray examination and the population to be examined. The unit had to be tested by a qualified expert using the technique charts. The credentials of all the operators, the supervisors and the Radiologists had to be submitted to the state. Results: All the appropriate documentation was sent to the state for review. The measured results between the Low Dose Protocol versus the default Adult Chest Protocol showed that there was a dose reduction of 65% for small (100-150 lb.) patient, 75% for the Medium patient (151-250 lbs.), and a 55% reduction for the Large patient ( over 250 lbs.). Conclusion: Measured results indicated that the Low Dose Protocol indeed lowered the screening patient's radiation dose and the institution was able to submit the protocol to the State's regulators.

  3. Three-Dimensions Segmentation of Pulmonary Vascular Trees for Low Dose CT Scans

    NASA Astrophysics Data System (ADS)

    Lai, Jun; Huang, Ying; Wang, Ying; Wang, Jun

    2016-12-01

    Due to the low contrast and the partial volume effects, providing an accurate and in vivo analysis for pulmonary vascular trees from low dose CT scans is a challenging task. This paper proposes an automatic integration segmentation approach for the vascular trees in low dose CT scans. It consists of the following steps: firstly, lung volumes are acquired by the knowledge based method from the CT scans, and then the data are smoothed by the 3D Gaussian filter; secondly, two or three seeds are gotten by the adaptive 2D segmentation and the maximum area selecting from different position scans; thirdly, each seed as the start voxel is inputted for a quick multi-seeds 3D region growing to get vascular trees; finally, the trees are refined by the smooth filter. Through skeleton analyzing for the vascular trees, the results show that the proposed method can provide much better and lower level vascular branches.

  4. Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

    SciTech Connect

    Tao, Yinghua; Chen, Guang-Hong; Hacker, Timothy A.; Raval, Amish N.; Van Lysel, Michael S.; Speidel, Michael A.

    2014-07-15

    Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937

  5. Improving low-dose cardiac CT images using 3D sparse representation based processing

    NASA Astrophysics Data System (ADS)

    Shi, Luyao; Chen, Yang; Luo, Limin

    2015-03-01

    Cardiac computed tomography (CCT) has been widely used in diagnoses of coronary artery diseases due to the continuously improving temporal and spatial resolution. When helical CT with a lower pitch scanning mode is used, the effective radiation dose can be significant when compared to other radiological exams. Many methods have been developed to reduce radiation dose in coronary CT exams including high pitch scans using dual source CT scanners and step-and-shot scanning mode for both single source and dual source CT scanners. Additionally, software methods have also been proposed to reduce noise in the reconstructed CT images and thus offering the opportunity to reduce radiation dose while maintaining the desired diagnostic performance of a certain imaging task. In this paper, we propose that low-dose scans should be considered in order to avoid the harm from accumulating unnecessary X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. Accordingly, in this paper, a 3D dictionary representation based image processing method is proposed to reduce CT image noise. Information on both spatial and temporal structure continuity is utilized in sparse representation to improve the performance of the image processing method. Clinical cases were used to validate the proposed method.

  6. Statistical image reconstruction for low-dose CT using nonlocal means-based regularization.

    PubMed

    Zhang, Hao; Ma, Jianhua; Wang, Jing; Liu, Yan; Lu, Hongbing; Liang, Zhengrong

    2014-09-01

    Low-dose computed tomography (CT) imaging without sacrifice of clinical tasks is desirable due to the growing concerns about excessive radiation exposure to the patients. One common strategy to achieve low-dose CT imaging is to lower the milliampere-second (mAs) setting in data scanning protocol. However, the reconstructed CT images by the conventional filtered back-projection (FBP) method from the low-mAs acquisitions may be severely degraded due to the excessive noise. Statistical image reconstruction (SIR) methods have shown potentials to significantly improve the reconstructed image quality from the low-mAs acquisitions, wherein the regularization plays a critical role and an established family of regularizations is based on the Markov random field (MRF) model. Inspired by the success of nonlocal means (NLM) in image processing applications, in this work, we propose to explore the NLM-based regularization for SIR to reconstruct low-dose CT images from low-mAs acquisitions. Experimental results with both digital and physical phantoms consistently demonstrated that SIR with the NLM-based regularization can achieve more gains than SIR with the well-known Gaussian MRF regularization or the generalized Gaussian MRF regularization and the conventional FBP method, in terms of image noise reduction and resolution preservation.

  7. Low-Dose X-ray CT Reconstruction via Dictionary Learning

    PubMed Central

    Xu, Qiong; Zhang, Lei; Hsieh, Jiang; Wang, Ge

    2013-01-01

    Although diagnostic medical imaging provides enormous benefits in the early detection and accuracy diagnosis of various diseases, there are growing concerns on the potential side effect of radiation induced genetic, cancerous and other diseases. How to reduce radiation dose while maintaining the diagnostic performance is a major challenge in the computed tomography (CT) field. Inspired by the compressive sensing theory, the sparse constraint in terms of total variation (TV) minimization has already led to promising results for low-dose CT reconstruction. Compared to the discrete gradient transform used in the TV method, dictionary learning is proven to be an effective way for sparse representation. On the other hand, it is important to consider the statistical property of projection data in the low-dose CT case. Recently, we have developed a dictionary learning based approach for low-dose X-ray CT. In this paper, we present this method in detail and evaluate it in experiments. In our method, the sparse constraint in terms of a redundant dictionary is incorporated into an objective function in a statistical iterative reconstruction framework. The dictionary can be either predetermined before an image reconstruction task or adaptively defined during the reconstruction process. An alternating minimization scheme is developed to minimize the objective function. Our approach is evaluated with low-dose X-ray projections collected in animal and human CT studies, and the improvement associated with dictionary learning is quantified relative to filtered backprojection and TV-based reconstructions. The results show that the proposed approach might produce better images with lower noise and more detailed structural features in our selected cases. However, there is no proof that this is true for all kinds of structures. PMID:22542666

  8. Low-dose X-ray CT reconstruction via dictionary learning.

    PubMed

    Xu, Qiong; Yu, Hengyong; Mou, Xuanqin; Zhang, Lei; Hsieh, Jiang; Wang, Ge

    2012-09-01

    Although diagnostic medical imaging provides enormous benefits in the early detection and accuracy diagnosis of various diseases, there are growing concerns on the potential side effect of radiation induced genetic, cancerous and other diseases. How to reduce radiation dose while maintaining the diagnostic performance is a major challenge in the computed tomography (CT) field. Inspired by the compressive sensing theory, the sparse constraint in terms of total variation (TV) minimization has already led to promising results for low-dose CT reconstruction. Compared to the discrete gradient transform used in the TV method, dictionary learning is proven to be an effective way for sparse representation. On the other hand, it is important to consider the statistical property of projection data in the low-dose CT case. Recently, we have developed a dictionary learning based approach for low-dose X-ray CT. In this paper, we present this method in detail and evaluate it in experiments. In our method, the sparse constraint in terms of a redundant dictionary is incorporated into an objective function in a statistical iterative reconstruction framework. The dictionary can be either predetermined before an image reconstruction task or adaptively defined during the reconstruction process. An alternating minimization scheme is developed to minimize the objective function. Our approach is evaluated with low-dose X-ray projections collected in animal and human CT studies, and the improvement associated with dictionary learning is quantified relative to filtered backprojection and TV-based reconstructions. The results show that the proposed approach might produce better images with lower noise and more detailed structural features in our selected cases. However, there is no proof that this is true for all kinds of structures. PMID:22542666

  9. Lung cancer screening with low-dose chest CT: current issues.

    PubMed

    Ahn, Myeong Im

    2004-06-01

    Computed tomography offers many advantages over routine radiographs in screening for lung cancer, and it is clear that low-dose spiral CT screening can more frequently find considerably smaller lung cancers than previous detection tools. Recently, investigators have performed low-dose spiral CT scanning for screening of lung cancer, and have suggested that CT screening can depict lung cancers at smaller sizes and at earlier stages. With technological advances in spiral CT scanners, the detection rate of small noncalcified pulmonary nodules has markedly increased, with higher rates noted with thinner collimation of CT scanning. Unfortunately, the majority of these have proved to be benign, i.e. false positive results. If, even in part, CT features could be found to predict benign nodules without follow-up, the false-positive rate would be reduced, and consequently, the cost, emotional stress, radiation dose, morbidity and mortality associated with interventional procedures would also be reduced. There have been several studies trying to establish reliable CT features for benign lesions in small pulmonary nodules and to determine their outcome. Although these efforts have not completely resolved the issue of false positive results, it is expected that lessons will be learnt on how to manage these small nodules through experience with screening in the near future. Because pulmonary nodules on CT are much more common in Korea than in western countries, the management algorithm for screening CT-detected nodules should be modified according to different circumstances, with consensus among related physicians and radiologists. In addition, to enhance patient care and avoid misunderstanding of inherent limitation of CT screening by the screening subjects, physicians, hospital managers as well as radiologists should provide proper information regarding CT screening to the screenees.

  10. Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

    NASA Astrophysics Data System (ADS)

    Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

    2012-03-01

    In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

  11. Investigation of iterative image reconstruction in low-dose breast CT

    NASA Astrophysics Data System (ADS)

    Bian, Junguo; Yang, Kai; Boone, John M.; Han, Xiao; Sidky, Emil Y.; Pan, Xiaochuan

    2014-06-01

    There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.

  12. A low dose simulation tool for CT systems with energy integrating detectors

    SciTech Connect

    Zabic, Stanislav; Morton, Thomas; Brown, Kevin M.; Wang Qiu

    2013-03-15

    Purpose: This paper introduces a new strategy for simulating low-dose computed tomography (CT) scans using real scans of a higher dose as an input. The tool is verified against simulations and real scans and compared to other approaches found in the literature. Methods: The conditional variance identity is used to properly account for the variance of the input high-dose data, and a formula is derived for generating a new Poisson noise realization which has the same mean and variance as the true low-dose data. The authors also derive a formula for the inclusion of real samples of detector noise, properly scaled according to the level of the simulated x-ray signals. Results: The proposed method is shown to match real scans in number of experiments. Noise standard deviation measurements in simulated low-dose reconstructions of a 35 cm water phantom match real scans in a range from 500 to 10 mA with less than 5% error. Mean and variance of individual detector channels are shown to match closely across the detector array. Finally, the visual appearance of noise and streak artifacts is shown to match in real scans even under conditions of photon-starvation (with tube currents as low as 10 and 80 mA). Additionally, the proposed method is shown to be more accurate than previous approaches (1) in achieving the correct mean and variance in reconstructed images from pure-Poisson noise simulations (with no detector noise) under photon-starvation conditions, and (2) in simulating the correct noise level and detector noise artifacts in real low-dose scans. Conclusions: The proposed method can accurately simulate low-dose CT data starting from high-dose data, including effects from photon starvation and detector noise. This is potentially a very useful tool in helping to determine minimum dose requirements for a wide range of clinical protocols and advanced reconstruction algorithms.

  13. A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

    SciTech Connect

    Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.

    2013-10-15

    Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

  14. [Ultra-low dose chest CT: The end of chest radiograph?].

    PubMed

    Ludes, Claire; Schaal, Marysa; Labani, Aissam; Jeung, Mi-Young; Roy, Catherine; Ohana, Mickaël

    2016-03-01

    Ultra-low dose chest CT (ULD-CT) is acquired at a radiation dose lowered to that of a PA and lateral chest X-ray. Its image quality is degraded, yet remains diagnostic in many clinical indications. Technological improvements, with iterative reconstruction at the foreground, allowed a strong increase in the image quality obtained with this examination, which is achievable on most recent (<5 years) scanner. Established clinical indications of ULD-CT are increasing, and its non-inferiority compared to the reference "full dose" chest CT are currently demonstrated for the detection of solid nodules, for asbestos-related pleural diseases screening and for the monitoring of infectious pneumonia. Its current limitations are the obese patients (BMI>35) and the interstitial pneumonia, situations in which their performances are insufficient. PMID:26830922

  15. Automated segmentation of cardiac visceral fat in low-dose non-contrast chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    Cardiac visceral fat was segmented from low-dose non-contrast chest CT images using a fully automated method. Cardiac visceral fat is defined as the fatty tissues surrounding the heart region, enclosed by the lungs and posterior to the sternum. It is measured by constraining the heart region with an Anatomy Label Map that contains robust segmentations of the lungs and other major organs and estimating the fatty tissue within this region. The algorithm was evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets. Based on visual inspection, 343 cases had good cardiac visceral fat segmentation. For quantitative evaluation, manual markings of cardiac visceral fat regions were made in 3 image slices for 45 low-dose scans and the Dice similarity coefficient (DSC) was computed. The automated algorithm achieved an average DSC of 0.93. Cardiac visceral fat volume (CVFV), heart region volume (HRV) and their ratio were computed for each case. The correlation between cardiac visceral fat measurement and coronary artery and aortic calcification was also evaluated. Results indicated the automated algorithm for measuring cardiac visceral fat volume may be an alternative method to the traditional manual assessment of thoracic region fat content in the assessment of cardiovascular disease risk.

  16. Automated detection and classification of interstitial lung diseases from low-dose CT images

    NASA Astrophysics Data System (ADS)

    Zheng, Bin; Leader, Joseph K.; Fuhrman, Carl R.; Sciurba, Frank C.; Gur, David

    2004-05-01

    We developed a computer-aided diagnosis (CAD) scheme to detect and quantitatively assess interstitial lung diseases (ILD) depicted on low-dose and multi-slice helical high-resolution computed tomography (CT) examinations. Eighteen CT cases acquired from patients who underwent routine low-dose whole-lung screening examinations for the detection of lung cancer were used to test the scheme. ILD was identified in all of these cases. The CAD scheme involves multiple steps to segment lung areas, identify suspicious ILD regions depicted on each CT slice, and generate volumetric ILD lesions by grouping and matching ILD regions detected on multiple adjacent slices. The scheme computes five "global" features for each identified ILD region, which include size (or volume), contrast, average local pixel value fluctuation, mean of stochastic fractal dimension, and geometric fractal dimension. Two sets of classification rules are applied to remove false-positive detections. The severity of ILD in each case was rated by one experienced chest radiologist into one of the three categories (mild, moderate, and severe). A distance-weighted k-nearest neighbor algorithm and round-robin validation method was applied to classify each testing case into one of the three categories of severity. In this experiment, the CAD scheme classified 78% (14 out of 18) cases into the same categories as rated by the radiologist.

  17. Computer-aided detection of early interstitial lung diseases using low-dose CT images

    NASA Astrophysics Data System (ADS)

    Park, Sang Cheol; Tan, Jun; Wang, Xingwei; Lederman, Dror; Leader, Joseph K.; Kim, Soo Hyung; Zheng, Bin

    2011-02-01

    This study aims to develop a new computer-aided detection (CAD) scheme to detect early interstitial lung disease (ILD) using low-dose computed tomography (CT) examinations. The CAD scheme classifies each pixel depicted on the segmented lung areas into positive or negative groups for ILD using a mesh-grid-based region growth method and a multi-feature-based artificial neural network (ANN). A genetic algorithm was applied to select optimal image features and the ANN structure. In testing each CT examination, only pixels selected by the mesh-grid region growth method were analyzed and classified by the ANN to improve computational efficiency. All unselected pixels were classified as negative for ILD. After classifying all pixels into the positive and negative groups, CAD computed a detection score based on the ratio of the number of positive pixels to all pixels in the segmented lung areas, which indicates the likelihood of the test case being positive for ILD. When applying to an independent testing dataset of 15 positive and 15 negative cases, the CAD scheme yielded the area under receiver operating characteristic curve (AUC = 0.884 ± 0.064) and 80.0% sensitivity at 85.7% specificity. The results demonstrated the feasibility of applying the CAD scheme to automatically detect early ILD using low-dose CT examinations.

  18. A Longitudinal Low Dose μCT Analysis of Bone Healing in Mice: A Pilot Study.

    PubMed

    Di, Lu-Zhao; Couture, Vanessa; Leblanc, Elisabeth; Alinejad, Yasaman; Beaudoin, Jean-François; Lecomte, Roger; Berthod, François; Faucheux, Nathalie; Balg, Frédéric; Grenier, Guillaume

    2014-01-01

    Low dose microcomputed tomography (μCT) is a recently matured technique that enables the study of longitudinal bone healing and the testing of experimental treatments for bone repair. This imaging technique has been used for studying craniofacial repair in mice but not in an orthopedic context. This is mainly due to the size of the defects (approximately 1.0 mm) in long bone, which heal rapidly and may thus negatively impact the assessment of the effectiveness of experimental treatments. We developed a longitudinal low dose μCT scan analysis method combined with a new image segmentation and extraction software using Hounsfield unit (HU) scores to quantitatively monitor bone healing in small femoral cortical defects in live mice. We were able to reproducibly quantify bone healing longitudinally over time with three observers. We used high speed intramedullary reaming to prolong healing in order to circumvent the rapid healing typical of small defects. Bone healing prolongation combined with μCT imaging to study small bone defects in live mice thus shows potential as a promising tool for future preclinical research on bone healing. PMID:25431676

  19. Automated measurement of pulmonary artery in low-dose non-contrast chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    A new measurement of the pulmonary artery diameter is obtained where the artery may be robustly segmented between the heart and the artery bifurcation. An automated algorithm is presented that can make this pulmonary artery measurement in low-dose non-contrast chest CT images. The algorithm uses a cylinder matching method following geometric constraints obtained from other adjacent organs that have been previously segmented. This new measurement and the related ratio of pulmonary artery to aortic artery measurement are compared to traditional manual approaches for pulmonary artery characterization. The algorithm was qualitatively evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets; 324 out of the 347 cases had good segmentations and in the other 23 cases there was significant boundary inaccuracy. For quantitative evaluation, the comparison was to manually marked pulmonary artery boundary in an axial slice in 45 cases; the resulting average Dice Similarity Coefficient was 0.88 (max 0.95, min 0.74). For the 45 cases with manual markings, the correlation between the automated pulmonary artery to ascending aorta diameter ratio and manual ratio at pulmonary artery bifurcation level was 0.81. Using Bland-Altman analysis, the mean difference of the two ratios was 0.03 and the limits of agreement was (-0.12, 0.18). This automated measurement may have utility as an alternative to the conventional manual measurement of pulmonary artery diameter at the bifurcation level especially in the context of noisy low-dose CT images.

  20. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms.

    PubMed

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M; Asma, Evren; Kinahan, Paul E; De Man, Bruno

    2015-10-01

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition.We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality.With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels

  1. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms.

    PubMed

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M; Asma, Evren; Kinahan, Paul E; De Man, Bruno

    2015-10-01

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition.We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality.With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels

  2. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms

    NASA Astrophysics Data System (ADS)

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M.; Asma, Evren; Kinahan, Paul E.; De Man, Bruno

    2015-09-01

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition. We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality. With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose

  3. Examination using modern low dose Multislice-CT (MS-CT) in otorhinolaryngology in a six-week-old baby.

    PubMed

    Heidelberg, Sokiranski R; Heidelberg, Plinkert M; Istanbul, Yildiz F; Ulm, Pirsig W

    2016-06-01

    A 6-week-old girl suffered from a growing and recurrently bleeding mass of unrecognizable origin, obstructing the left nose. Using low-dose Multislice-CT the exact diagnostic localization could be found within one minute in the sleeping baby without sedation or general anesthesia. The result of this imaging enabled the successful complete microscopic removal of a hemangioma from the left inferior turbinate. Follow-up after 15 months showed normal nasal finds.

  4. Evaluation of a low-dose CT protocol with oral contrast for assessment of acute appendicitis.

    PubMed

    Platon, Alexandra; Jlassi, Helmi; Rutschmann, Olivier T; Becker, Christoph D; Verdun, Francis R; Gervaz, Pascal; Poletti, Pierre-Alexandre

    2009-02-01

    The aim of this study was to evaluate a low-dose CT with oral contrast medium (LDCT) for the diagnosis of acute appendicitis and compare its performance with standard-dose i.v. contrast-enhanced CT (standard CT) according to patients' BMIs. Eighty-six consecutive patients admitted with suspicion of acute appendicitis underwent LDCT (30 mAs), followed by standard CT (180 mAs). Both examinations were reviewed by two experienced radiologists for direct and indirect signs of appendicitis. Clinical and surgical follow-up was considered as the reference standard. Appendicitis was confirmed by surgery in 37 (43%) of the 86 patients. Twenty-nine (34%) patients eventually had an alternative discharge diagnosis to explain their abdominal pain. Clinical and biological follow-up was uneventful in 20 (23%) patients. LDCT and standard CT had the same sensitivity (100%, 33/33) and specificity (98%, 45/46) to diagnose appendicitis in patients with a body mass index (BMI) >or= 18.5. In slim patients (BMI<18.5), sensitivity to diagnose appendicitis was 50% (2/4) for LDCT and 100% (4/4) for standard CT, while specificity was identical for both techniques (67%, 2/3). LDCT may play a role in the diagnostic workup of patients with a BMI >or= 18.5.

  5. Texture-preserving Bayesian image reconstruction for low-dose CT

    NASA Astrophysics Data System (ADS)

    Zhang, Hao; Han, Hao; Hu, Yifan; Liu, Yan; Ma, Jianhua; Li, Lihong; Moore, William; Liang, Zhengrong

    2016-03-01

    Markov random field (MRF) model has been widely used in Bayesian image reconstruction to reconstruct piecewise smooth images in the presence of noise, such as in low-dose X-ray computed tomography (LdCT). While it can preserve edge sharpness via edge-preserving potential function, its regional smoothing may sacrifice tissue image textures, which have been recognized as useful imaging biomarkers, and thus it compromises clinical tasks such as differentiating malignant vs. benign lesions, e.g., lung nodule or colon polyp. This study aims to shift the edge preserving regional noise smoothing paradigm to texture-preserving framework for LdCT image reconstruction while retaining the advantage of MRF's neighborhood system on edge preservation. Specifically, we adapted the MRF model to incorporate the image textures of lung, bone, fat, muscle, etc. from previous full-dose CT scan as a priori knowledge for texture-preserving Bayesian reconstruction of current LdCT images. To show the feasibility of proposed reconstruction framework, experiments using clinical patient scans (with lung nodule or colon polyp) were conducted. The experimental outcomes showed noticeable gain by the a priori knowledge for LdCT image reconstruction with the well-known Haralick texture measures. Thus, it is conjectured that texture-preserving LdCT reconstruction has advantages over edge-preserving regional smoothing paradigm for texture-specific clinical applications.

  6. [Examination of Visual Effect in Low-dose Cerebral CT Perfusion Phantom Image Using Iterative Reconstruction].

    PubMed

    Ohmura, Tomomi; Lee, Yongbum; Takahashi, Noriyuki; Sato, Yuichiro; Ishida, Takato; Toyoshima, Hideto

    2015-11-01

    CT perfusion (CTP) is obtained cerebrovascular circulation image for assessment of stroke patients; however, at the expense of increased radiation dose by dynamic scan. Iterative reconstruction (IR) method is possible to decrease image noise, it has the potential to reduce radiation dose. The purpose of this study is to assess the visual effect of IR method by using a digital perfusion phantom. The digital perfusion phantom was created by reconstructed filtered back projection (FBP) method and IR method CT images that had five exposure doses. Various exposure dose cerebral blood flow (CBF) images were derived from deconvolution algorithm. Contrast-to-noise ratio (CNR) and visual assessment were compared among the various exposure dose and each reconstructions. Result of low exposure dose with IR method showed, compared with FBP method, high CNR in severe ischemic area, and visual assessment was significantly improvement. IR method is useful for improving image quality of low-dose CTP. PMID:26596197

  7. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    NASA Astrophysics Data System (ADS)

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-03-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

  8. Median prior constrained TV algorithm for sparse view low-dose CT reconstruction.

    PubMed

    Liu, Yi; Shangguan, Hong; Zhang, Quan; Zhu, Hongqing; Shu, Huazhong; Gui, Zhiguo

    2015-05-01

    It is known that lowering the X-ray tube current (mAs) or tube voltage (kVp) and simultaneously reducing the total number of X-ray views (sparse view) is an effective means to achieve low-dose in computed tomography (CT) scan. However, the associated image quality by the conventional filtered back-projection (FBP) usually degrades due to the excessive quantum noise. Although sparse-view CT reconstruction algorithm via total variation (TV), in the scanning protocol of reducing X-ray tube current, has been demonstrated to be able to result in significant radiation dose reduction while maintain image quality, noticeable patchy artifacts still exist in reconstructed images. In this study, to address the problem of patchy artifacts, we proposed a median prior constrained TV regularization to retain the image quality by introducing an auxiliary vector m in register with the object. Specifically, the approximate action of m is to draw, in each iteration, an object voxel toward its own local median, aiming to improve low-dose image quality with sparse-view projection measurements. Subsequently, an alternating optimization algorithm is adopted to optimize the associative objective function. We refer to the median prior constrained TV regularization as "TV_MP" for simplicity. Experimental results on digital phantoms and clinical phantom demonstrated that the proposed TV_MP with appropriate control parameters can not only ensure a higher signal to noise ratio (SNR) of the reconstructed image, but also its resolution compared with the original TV method.

  9. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    PubMed Central

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-01-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images. PMID:26980176

  10. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation.

    PubMed

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-03-16

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

  11. Effects of sparse sampling schemes on image quality in low-dose CT

    SciTech Connect

    Abbas, Sajid; Lee, Taewon; Cho, Seungryong; Shin, Sukyoung; Lee, Rena

    2013-11-15

    Purpose: Various scanning methods and image reconstruction algorithms are actively investigated for low-dose computed tomography (CT) that can potentially reduce a health-risk related to radiation dose. Particularly, compressive-sensing (CS) based algorithms have been successfully developed for reconstructing images from sparsely sampled data. Although these algorithms have shown promises in low-dose CT, it has not been studied how sparse sampling schemes affect image quality in CS-based image reconstruction. In this work, the authors present several sparse-sampling schemes for low-dose CT, quantitatively analyze their data property, and compare effects of the sampling schemes on the image quality.Methods: Data properties of several sampling schemes are analyzed with respect to the CS-based image reconstruction using two measures: sampling density and data incoherence. The authors present five different sparse sampling schemes, and simulated those schemes to achieve a targeted dose reduction. Dose reduction factors of about 75% and 87.5%, compared to a conventional scan, were tested. A fully sampled circular cone-beam CT data set was used as a reference, and sparse sampling has been realized numerically based on the CBCT data.Results: It is found that both sampling density and data incoherence affect the image quality in the CS-based reconstruction. Among the sampling schemes the authors investigated, the sparse-view, many-view undersampling (MVUS)-fine, and MVUS-moving cases have shown promising results. These sampling schemes produced images with similar image quality compared to the reference image and their structure similarity index values were higher than 0.92 in the mouse head scan with 75% dose reduction.Conclusions: The authors found that in CS-based image reconstructions both sampling density and data incoherence affect the image quality, and suggest that a sampling scheme should be devised and optimized by use of these indicators. With this strategic

  12. Evaluation of a low-dose/slow-rotating SPECT-CT system

    NASA Astrophysics Data System (ADS)

    Hamann, M.; Aldridge, M.; Dickson, J.; Endozo, R.; Lozhkin, K.; Hutton, B. F.

    2008-05-01

    The 4-slice CT that forms part of the GE Infinia Hawkeye-4 SPECT-CT scanner (Hawkeye) is evaluated against the diagnostic 16-slice CT that is incorporated in the GE Discovery ST PET-CT system (DST). The x-ray tube of the slow-rotating Hawkeye system (23 s/rotation) operates at approximately a third of the dose of diagnostic systems as used for conventional diagnostic imaging. Image reconstruction is optimized for low noise. High-contrast spatial resolution significantly falls behind diagnostic figures: the average of MTF50 and MTF10 (resolution where the MTF has fallen to 50% and 10%) is 2.8 ± 0.1 cm-1 for Hawkeye and 5.3 ± 0.1 cm-1 for the DST (standard reconstruction filters). Resolution in the direction of the couch movement (z coordinate) is governed by the fixed Hawkeye slice width of 5 mm. Reconstruction accuracy is found to be increased by reducing the default z increment from 4.4 mm to 2.2 mm. Low-contrast object detectability is superior compared with diagnostic systems operating in the Hawkeye dose range. In the diagnostic dose regime, however, small low-contrast details remain visible in DST that are not detectable with Hawkeye. Although not of diagnostic quality, the low-dose Hawkeye provides appropriate data for SPECT attenuation correction and anatomical localization capability. For more information on this article, see medicalphysicsweb.org

  13. Low-dose CT for quantitative analysis in acute respiratory distress syndrome

    PubMed Central

    2013-01-01

    Introduction The clinical use of serial quantitative computed tomography (CT) to characterize lung disease and guide the optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) is limited by the risk of cumulative radiation exposure and by the difficulties and risks related to transferring patients to the CT room. We evaluated the effects of tube current-time product (mAs) variations on quantitative results in healthy lungs and in experimental ARDS in order to support the use of low-dose CT for quantitative analysis. Methods In 14 sheep chest CT was performed at baseline and after the induction of ARDS via intravenous oleic acid injection. For each CT session, two consecutive scans were obtained applying two different mAs: 60 mAs was paired with 140, 15 or 7.5 mAs. All other CT parameters were kept unaltered (tube voltage 120 kVp, collimation 32 × 0.5 mm, pitch 0.85, matrix 512 × 512, pixel size 0.625 × 0.625 mm). Quantitative results obtained at different mAs were compared via Bland-Altman analysis. Results Good agreement was observed between 60 mAs and 140 mAs and between 60 mAs and 15 mAs (all biases less than 1%). A further reduction of mAs to 7.5 mAs caused an increase in the bias of poorly aerated and nonaerated tissue (-2.9% and 2.4%, respectively) and determined a significant widening of the limits of agreement for the same compartments (-10.5% to 4.8% for poorly aerated tissue and -5.9% to 10.8% for nonaerated tissue). Estimated mean effective dose at 140, 60, 15 and 7.5 mAs corresponded to 17.8, 7.4, 2.0 and 0.9 mSv, respectively. Image noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield units, respectively. Conclusions A reduction of effective dose up to 70% has been achieved with minimal effects on lung quantitative results. Low-dose computed tomography provides accurate quantitative results and could be used to characterize lung compartment distribution and

  14. Sinogram restoration for ultra-low-dose x-ray multi-slice helical CT by nonparametric regression

    NASA Astrophysics Data System (ADS)

    Jiang, Lu; Siddiqui, Khan; Zhu, Bin; Tao, Yang; Siegel, Eliot

    2007-03-01

    During the last decade, x-ray computed tomography (CT) has been applied to screen large asymptomatic smoking and nonsmoking populations for early lung cancer detection. Because a larger population will be involved in such screening exams, more and more attention has been paid to studying low-dose, even ultra-low-dose x-ray CT. However, reducing CT radiation exposure will increase noise level in the sinogram, thereby degrading the quality of reconstructed CT images as well as causing more streak artifacts near the apices of the lung. Thus, how to reduce the noise levels and streak artifacts in the low-dose CT images is becoming a meaningful topic. Since multi-slice helical CT has replaced conventional stop-and-shoot CT in many clinical applications, this research mainly focused on the noise reduction issue in multi-slice helical CT. The experiment data were provided by Siemens SOMATOM Sensation 16-Slice helical CT. It included both conventional CT data acquired under 120 kvp voltage and 119 mA current and ultra-low-dose CT data acquired under 120 kvp and 10 mA protocols. All other settings are the same as that of conventional CT. In this paper, a nonparametric smoothing method with thin plate smoothing splines and the roughness penalty was proposed to restore the ultra-low-dose CT raw data. Each projection frame was firstly divided into blocks, and then the 2D data in each block was fitted to a thin-plate smoothing splines' surface via minimizing a roughness-penalized least squares objective function. By doing so, the noise in each ultra-low-dose CT projection was reduced by leveraging the information contained not only within each individual projection profile, but also among nearby profiles. Finally the restored ultra-low-dose projection data were fed into standard filtered back projection (FBP) algorithm to reconstruct CT images. The rebuilt results as well as the comparison between proposed approach and traditional method were given in the results and

  15. A framework of whole heart extracellular volume fraction estimation for low dose cardiac CT images

    NASA Astrophysics Data System (ADS)

    Chen, Xinjian; Summers, Ronald M.; Nacif, Marcelo Souto; Liu, Songtao; Bluemke, David A.; Yao, Jianhua

    2012-02-01

    Cardiac magnetic resonance imaging (CMRI) has been well validated and allows quantification of myocardial fibrosis in comparison to overall mass of the myocardium. Unfortunately, CMRI is relatively expensive and is contraindicated in patients with intracardiac devices. Cardiac CT (CCT) is widely available and has been validated for detection of scar and myocardial stress/rest perfusion. In this paper, we sought to evaluate the potential of low dose CCT for the measurement of myocardial whole heart extracellular volume (ECV) fraction. A novel framework was proposed for CCT whole heart ECV estimation, which consists of three main steps. First, a shape constrained graph cut (GC) method was proposed for myocardium and blood pool segmentation for post-contrast image. Second, the symmetric Demons deformable registrations method was applied to register pre-contrast to post-contrast images. Finally, the whole heart ECV value was computed. The proposed method was tested on 7 clinical low dose CCT datasets with pre-contrast and post-contrast images. The preliminary results demonstrated the feasibility and efficiency of the proposed method.

  16. Effect of low-dose CT and iterative reconstruction on trabecular bone microstructure assessment

    NASA Astrophysics Data System (ADS)

    Kopp, Felix K.; Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Bauer, Jan S.; Noël, Peter B.

    2016-03-01

    The trabecular bone microstructure is an important factor in the development of osteoporosis. It is well known that its deterioration is one effect when osteoporosis occurs. Previous research showed that the analysis of trabecular bone microstructure enables more precise diagnoses of osteoporosis compared to a sole measurement of the mineral density. Microstructure parameters are assessed on volumetric images of the bone acquired either with high-resolution magnetic resonance imaging, high-resolution peripheral quantitative computed tomography or high-resolution computed tomography (CT), with only CT being applicable to the spine, which is one of clinically most relevant fracture sites. However, due to the high radiation exposure for imaging the whole spine these measurements are not applicable in current clinical routine. In this work, twelve vertebrae from three different donors were scanned with standard and low radiation dose. Trabecular bone microstructure parameters were assessed for CT images reconstructed with statistical iterative reconstruction (SIR) and analytical filtered backprojection (FBP). The resulting structure parameters were correlated to the biomechanically determined fracture load of each vertebra. Microstructure parameters assessed for low-dose data reconstructed with SIR significantly correlated with fracture loads as well as parameters assessed for standard-dose data reconstructed with FBP. Ideal results were achieved with low to zero regularization strength yielding microstructure parameters not significantly different from those assessed for standard-dose FPB data. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

  17. Optimized Parallelization for Nonlocal Means Based Low Dose CT Image Processing.

    PubMed

    Zhang, Libo; Yang, Benqiang; Zhuang, Zhikun; Hu, Yining; Chen, Yang; Luo, Limin; Shu, Huazhong

    2015-01-01

    Low dose CT (LDCT) images are often significantly degraded by severely increased mottled noise/artifacts, which can lead to lowered diagnostic accuracy in clinic. The nonlocal means (NLM) filtering can effectively remove mottled noise/artifacts by utilizing large-scale patch similarity information in LDCT images. But the NLM filtering application in LDCT imaging also requires high computation cost because intensive patch similarity calculation within a large searching window is often required to be used to include enough structure-similarity information for noise/artifact suppression. To improve its clinical feasibility, in this study we further optimize the parallelization of NLM filtering by avoiding the repeated computation with the row-wise intensity calculation and the symmetry weight calculation. The shared memory with fast I/O speed is also used in row-wise intensity calculation for the proposed method. Quantitative experiment demonstrates that significant acceleration can be achieved with respect to the traditional straight pixel-wise parallelization.

  18. Low-dose CT reconstruction via edge-preserving total variation regularization

    NASA Astrophysics Data System (ADS)

    Tian, Zhen; Jia, Xun; Yuan, Kehong; Pan, Tinsu; Jiang, Steve B.

    2011-09-01

    High radiation dose in computed tomography (CT) scans increases the lifetime risk of cancer and has become a major clinical concern. Recently, iterative reconstruction algorithms with total variation (TV) regularization have been developed to reconstruct CT images from highly undersampled data acquired at low mAs levels in order to reduce the imaging dose. Nonetheless, the low-contrast structures tend to be smoothed out by the TV regularization, posing a great challenge for the TV method. To solve this problem, in this work we develop an iterative CT reconstruction algorithm with edge-preserving TV (EPTV) regularization to reconstruct CT images from highly undersampled data obtained at low mAs levels. The CT image is reconstructed by minimizing energy consisting of an EPTV norm and a data fidelity term posed by the x-ray projections. The EPTV term is proposed to preferentially perform smoothing only on the non-edge part of the image in order to better preserve the edges, which is realized by introducing a penalty weight to the original TV norm. During the reconstruction process, the pixels at the edges would be gradually identified and given low penalty weight. Our iterative algorithm is implemented on graphics processing unit to improve its speed. We test our reconstruction algorithm on a digital NURBS-based cardiac-troso phantom, a physical chest phantom and a Catphan phantom. Reconstruction results from a conventional filtered backprojection (FBP) algorithm and a TV regularization method without edge-preserving penalty are also presented for comparison purposes. The experimental results illustrate that both the TV-based algorithm and our EPTV algorithm outperform the conventional FBP algorithm in suppressing the streaking artifacts and image noise under a low-dose context. Our edge-preserving algorithm is superior to the TV-based algorithm in that it can preserve more information of low-contrast structures and therefore maintain acceptable spatial resolution.

  19. Heart region segmentation from low-dose CT scans: an anatomy based approach

    NASA Astrophysics Data System (ADS)

    Reeves, Anthony P.; Biancardi, Alberto M.; Yankelevitz, David F.; Cham, Matthew D.; Henschke, Claudia I.

    2012-02-01

    Cardiovascular disease is a leading cause of death in developed countries. The concurrent detection of heart diseases during low-dose whole-lung CT scans (LDCT), typically performed as part of a screening protocol, hinges on the accurate quantification of coronary calcification. The creation of fully automated methods is ideal as complete manual evaluation is imprecise, operator dependent, time consuming and thus costly. The technical challenges posed by LDCT scans in this context are mainly twofold. First, there is a high level image noise arising from the low radiation dose technique. Additionally, there is a variable amount of cardiac motion blurring due to the lack of electrocardiographic gating and the fact that heart rates differ between human subjects. As a consequence, the reliable segmentation of the heart, the first stage toward the implementation of morphologic heart abnormality detection, is also quite challenging. An automated computer method based on a sequential labeling of major organs and determination of anatomical landmarks has been evaluated on a public database of LDCT images. The novel algorithm builds from a robust segmentation of the bones and airways and embodies a stepwise refinement starting at the top of the lungs where image noise is at its lowest and where the carina provides a good calibration landmark. The segmentation is completed at the inferior wall of the heart where extensive image noise is accommodated. This method is based on the geometry of human anatomy and does not involve training through manual markings. Using visual inspection by an expert reader as a gold standard, the algorithm achieved successful heart and major vessel segmentation in 42 of 45 low-dose CT images. In the 3 remaining cases, the cardiac base was over segmented due to incorrect hemidiaphragm localization.

  20. Optimization of SPECT-CT Hybrid Imaging Using Iterative Image Reconstruction for Low-Dose CT: A Phantom Study

    PubMed Central

    Grosser, Oliver S.; Kupitz, Dennis; Ruf, Juri; Czuczwara, Damian; Steffen, Ingo G.; Furth, Christian; Thormann, Markus; Loewenthal, David; Ricke, Jens; Amthauer, Holger

    2015-01-01

    Background Hybrid imaging combines nuclear medicine imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) with computed tomography (CT). Through this hybrid design, scanned patients accumulate radiation exposure from both applications. Imaging modalities have been the subject of long-term optimization efforts, focusing on diagnostic applications. It was the aim of this study to investigate the influence of an iterative CT image reconstruction algorithm (ASIR) on the image quality of the low-dose CT images. Methodology/Principal Findings Examinations were performed with a SPECT-CT scanner with standardized CT and SPECT-phantom geometries and CT protocols with systematically reduced X-ray tube currents. Analyses included image quality with respect to photon flux. Results were compared to the standard FBP reconstructed images. The general impact of the CT-based attenuation maps used during SPECT reconstruction was examined for two SPECT phantoms. Using ASIR for image reconstructions, image noise was reduced compared to FBP reconstructions for the same X-ray tube current. The Hounsfield unit (HU) values reconstructed by ASIR were correlated to the FBP HU values(R2 ≥ 0.88) and the contrast-to-noise ratio (CNR) was improved by ASIR. However, for a phantom with increased attenuation, the HU values shifted for low X-ray tube currents I ≤ 60 mA (p ≤ 0.04). In addition, the shift of the HU values was observed within the attenuation corrected SPECT images for very low X-ray tube currents (I ≤ 20 mA, p ≤ 0.001). Conclusion/Significance In general, the decrease in X-ray tube current up to 30 mA in combination with ASIR led to a reduction of CT-related radiation exposure without a significant decrease in image quality. PMID:26390216

  1. Adaptive Tensor-Based Principal Component Analysis for Low-Dose CT Image Denoising

    PubMed Central

    Ai, Danni; Yang, Jian; Fan, Jingfan; Cong, Weijian; Wang, Yongtian

    2015-01-01

    Computed tomography (CT) has a revolutionized diagnostic radiology but involves large radiation doses that directly impact image quality. In this paper, we propose adaptive tensor-based principal component analysis (AT-PCA) algorithm for low-dose CT image denoising. Pixels in the image are presented by their nearby neighbors, and are modeled as a patch. Adaptive searching windows are calculated to find similar patches as training groups for further processing. Tensor-based PCA is used to obtain transformation matrices, and coefficients are sequentially shrunk by the linear minimum mean square error. Reconstructed patches are obtained, and a denoised image is finally achieved by aggregating all of these patches. The experimental results of the standard test image show that the best results are obtained with two denoising rounds according to six quantitative measures. For the experiment on the clinical images, the proposed AT-PCA method can suppress the noise, enhance the edge, and improve the image quality more effectively than NLM and KSVD denoising methods. PMID:25993566

  2. Deformable 3D-2D registration for CT and its application to low dose tomographic fluoroscopy

    NASA Astrophysics Data System (ADS)

    Flach, Barbara; Brehm, Marcus; Sawall, Stefan; Kachelrieß, Marc

    2014-12-01

    Many applications in medical imaging include image registration for matching of images from the same or different modalities. In the case of full data sampling, the respective reconstructed images are usually of such a good image quality that standard deformable volume-to-volume (3D-3D) registration approaches can be applied. But research in temporal-correlated image reconstruction and dose reductions increases the number of cases where rawdata are available from only few projection angles. Here, deteriorated image quality leads to non-acceptable deformable volume-to-volume registration results. Therefore a registration approach is required that is robust against a decreasing number of projections defining the target position. We propose a deformable volume-to-rawdata (3D-2D) registration method that aims at finding a displacement vector field maximizing the alignment of a CT volume and the acquired rawdata based on the sum of squared differences in rawdata domain. The registration is constrained by a regularization term in accordance with a fluid-based diffusion. Both cost function components, the rawdata fidelity and the regularization term, are optimized in an alternating manner. The matching criterion is optimized by a conjugate gradient descent for nonlinear functions, while the regularization is realized by convolution of the vector fields with Gaussian kernels. We validate the proposed method and compare it to the demons algorithm, a well-known 3D-3D registration method. The comparison is done for a range of 4-60 target projections using datasets from low dose tomographic fluoroscopy as an application example. The results show a high correlation to the ground truth target position without introducing artifacts even in the case of very few projections. In particular the matching in the rawdata domain is improved compared to the 3D-3D registration for the investigated range. The proposed volume-to-rawdata registration increases the robustness regarding sparse

  3. Deformable 3D-2D registration for CT and its application to low dose tomographic fluoroscopy.

    PubMed

    Flach, Barbara; Brehm, Marcus; Sawall, Stefan; Kachelrieß, Marc

    2014-12-21

    Many applications in medical imaging include image registration for matching of images from the same or different modalities. In the case of full data sampling, the respective reconstructed images are usually of such a good image quality that standard deformable volume-to-volume (3D-3D) registration approaches can be applied. But research in temporal-correlated image reconstruction and dose reductions increases the number of cases where rawdata are available from only few projection angles. Here, deteriorated image quality leads to non-acceptable deformable volume-to-volume registration results. Therefore a registration approach is required that is robust against a decreasing number of projections defining the target position. We propose a deformable volume-to-rawdata (3D-2D) registration method that aims at finding a displacement vector field maximizing the alignment of a CT volume and the acquired rawdata based on the sum of squared differences in rawdata domain. The registration is constrained by a regularization term in accordance with a fluid-based diffusion. Both cost function components, the rawdata fidelity and the regularization term, are optimized in an alternating manner. The matching criterion is optimized by a conjugate gradient descent for nonlinear functions, while the regularization is realized by convolution of the vector fields with Gaussian kernels. We validate the proposed method and compare it to the demons algorithm, a well-known 3D-3D registration method. The comparison is done for a range of 4-60 target projections using datasets from low dose tomographic fluoroscopy as an application example. The results show a high correlation to the ground truth target position without introducing artifacts even in the case of very few projections. In particular the matching in the rawdata domain is improved compared to the 3D-3D registration for the investigated range. The proposed volume-to-rawdata registration increases the robustness regarding sparse

  4. Texture-based CAD improves diagnosis for low-dose CT colonography

    NASA Astrophysics Data System (ADS)

    Liang, Zhengrong; Cohen, Harris; Posniak, Erica; Fiore, Eddie; Wang, Zigang; Li, Bin; Andersen, Joseph; Harrington, Donald

    2008-03-01

    Computed tomography (CT)-based virtual colonoscopy or CT colonography (CTC) currently utilizes oral contrast solutions to tag the colonic fluid and possibly residual stool for differentiation from the colon wall and polyps. The enhanced image density of the tagged colonic materials causes a significant partial volume (PV) effect into the colon wall as well as the lumen space (filled with air or CO II). The PV effect on the colon wall can "bury" polyps of size as large as 5mm by increasing their image densities to a noticeable level, resulting in false negatives. It can also create false positives when PV effect goes into the lumen space. We have been modeling the PV effect for mixture-based image segmentation and developing text-based computer-aided detection of polyp (CADpolyp) by utilizing the PV mixture-based image segmentation. This work presents some preliminary results of developing and applying texture-based CADpolyp technique to low-dose CTC studies. A total of 114 studies of asymptomatic patients older than 50, who underwent CTC and then optical colonoscopy (OC) on the same day, were selected from a database, which was accumulated in the past decade and contains various bowel preparations and CT scanning protocols. The participating radiologists found ten polyps of greater than 5 mm from a total of 16 OC proved polyps, i.e., a detection sensitivity of 63%. They scored 23 false positives from the database, i.e., a 20% false positive rate. Approximately 70% of the datasets were marked as imperfect bowel cleansing and/or presence of image artifacts. The impact of imperfect bowel cleansing and image artifacts on VC performance is significant. The texture-based CADpolyp detected all the polyps with an average of 2.68 false positives per patient. This indicates that texture-based CADpolyp can improve the CTC performance in the cases of imperfect cleansed bowels and presence of image artifacts.

  5. Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

    2015-09-01

    Due to the limited spatial resolution, partial volume effect has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with 99mTc-tetrofosmin, a myocardial perfusion agent, and 99mTc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of 99mTc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both 99mTc-tetrofosmin perfusion imaging and 99mTc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly for low

  6. Anatomical-based Partial Volume Correction for Low-dose Dedicated Cardiac SPECT/CT

    PubMed Central

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

    2016-01-01

    Due to the limited spatial resolution, partial volume effect (PVE) has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view (FOV) over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation Geometry Transfer Matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with 99mTc-tetrofosmin, a myocardial perfusion agent, and 99mTc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of 99mTc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both 99mTc-tetrofosmin perfusion imaging and 99mTc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly

  7. Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT.

    PubMed

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R; Sinusas, Albert J; Liu, Chi

    2015-09-01

    Due to the limited spatial resolution, partial volume effect has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with (99m)Tc-tetrofosmin, a myocardial perfusion agent, and (99m)Tc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of (99m)Tc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both (99m)Tc-tetrofosmin perfusion imaging and (99m)Tc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly

  8. Quantification of pulmonary vessel diameter in low-dose CT images

    NASA Astrophysics Data System (ADS)

    Rudyanto, Rina D.; Ortiz de Solórzano, Carlos; Muñoz-Barrutia, Arrate

    2015-03-01

    Accurate quantification of vessel diameter in low-dose Computer Tomography (CT) images is important to study pulmonary diseases, in particular for the diagnosis of vascular diseases and the characterization of morphological vascular remodeling in Chronic Obstructive Pulmonary Disease (COPD). In this study, we objectively compare several vessel diameter estimation methods using a physical phantom. Five solid tubes of differing diameters (from 0.898 to 3.980 mm) were embedded in foam, simulating vessels in the lungs. To measure the diameters, we first extracted the vessels using either of two approaches: vessel enhancement using multi-scale Hessian matrix computation, or explicitly segmenting them using intensity threshold. We implemented six methods to quantify the diameter: three estimating diameter as a function of scale used to calculate the Hessian matrix; two calculating equivalent diameter from the crosssection area obtained by thresholding the intensity and vesselness response, respectively; and finally, estimating the diameter of the object using the Full Width Half Maximum (FWHM). We find that the accuracy of frequently used methods estimating vessel diameter from the multi-scale vesselness filter depends on the range and the number of scales used. Moreover, these methods still yield a significant error margin on the challenging estimation of the smallest diameter (on the order or below the size of the CT point spread function). Obviously, the performance of the thresholding-based methods depends on the value of the threshold. Finally, we observe that a simple adaptive thresholding approach can achieve a robust and accurate estimation of the smallest vessels diameter.

  9. Segmentation of the whole breast from low-dose chest CT images

    NASA Astrophysics Data System (ADS)

    Liu, Shuang; Salvatore, Mary; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    The segmentation of whole breast serves as the first step towards automated breast lesion detection. It is also necessary for automatically assessing the breast density, which is considered to be an important risk factor for breast cancer. In this paper we present a fully automated algorithm to segment the whole breast in low-dose chest CT images (LDCT), which has been recommended as an annual lung cancer screening test. The automated whole breast segmentation and potential breast density readings as well as lesion detection in LDCT will provide useful information for women who have received LDCT screening, especially the ones who have not undergone mammographic screening, by providing them additional risk indicators for breast cancer with no additional radiation exposure. The two main challenges to be addressed are significant range of variations in terms of the shape and location of the breast in LDCT and the separation of pectoral muscles from the glandular tissues. The presented algorithm achieves robust whole breast segmentation using an anatomy directed rule-based method. The evaluation is performed on 20 LDCT scans by comparing the segmentation with ground truth manually annotated by a radiologist on one axial slice and two sagittal slices for each scan. The resulting average Dice coefficient is 0.880 with a standard deviation of 0.058, demonstrating that the automated segmentation algorithm achieves results consistent with manual annotations of a radiologist.

  10. Lung Cancer Screening With Low-Dose CT in the United States.

    PubMed

    Eberth, Jan M

    2015-12-01

    The findings of the landmark National Lung Screening Trial (NLST)-showing a 20% reduction in lung cancer mortality when screening with low-dose CT (LDCT), compared with chest radiography-marked a turning point in the field of lung cancer screening, influencing organizational recommendations and leading to increasing acceptance of LDCT for screening of individuals at high risk for lung cancer. However, many practices and institutions have experienced barriers in their attempts to implement successful screening programs; these include challenges in maintaining the same high caliber of screening programs as those in the NLST, confusion regarding insurance reimbursement protocols, and a lack of resources to help physicians discuss the specifics of LDCT screening with their patients. To address these challenges, standards are being established to ensure consistent quality of screening programs, including certification standards and protocols maintained by the ACR. In addition, the US Preventive Services Task Force's "B" rating, given to LDCT screening in late 2013, resulted in mandated private insurance coverage beginning in 2015 and the 2015 CMS coverage determination has spurred previously reluctant organizations to prepare for population-based screening. Despite these successes, protocols for billing and claims processing are still evolving and organizations are considering how best to implement the shared decision-making process required by CMS. Despite some procedural setbacks that have yet to be resolved, LDCT screening for individuals at high risk of lung cancer has grown substantially since its effectiveness was shown by the NLST in 2011. PMID:26614885

  11. Optimized Parallelization for Nonlocal Means Based Low Dose CT Image Processing.

    PubMed

    Zhang, Libo; Yang, Benqiang; Zhuang, Zhikun; Hu, Yining; Chen, Yang; Luo, Limin; Shu, Huazhong

    2015-01-01

    Low dose CT (LDCT) images are often significantly degraded by severely increased mottled noise/artifacts, which can lead to lowered diagnostic accuracy in clinic. The nonlocal means (NLM) filtering can effectively remove mottled noise/artifacts by utilizing large-scale patch similarity information in LDCT images. But the NLM filtering application in LDCT imaging also requires high computation cost because intensive patch similarity calculation within a large searching window is often required to be used to include enough structure-similarity information for noise/artifact suppression. To improve its clinical feasibility, in this study we further optimize the parallelization of NLM filtering by avoiding the repeated computation with the row-wise intensity calculation and the symmetry weight calculation. The shared memory with fast I/O speed is also used in row-wise intensity calculation for the proposed method. Quantitative experiment demonstrates that significant acceleration can be achieved with respect to the traditional straight pixel-wise parallelization. PMID:26078781

  12. Optimized Parallelization for Nonlocal Means Based Low Dose CT Image Processing

    PubMed Central

    Zhang, Libo; Yang, Benqiang; Zhuang, Zhikun; Hu, Yining; Chen, Yang; Luo, Limin; Shu, Huazhong

    2015-01-01

    Low dose CT (LDCT) images are often significantly degraded by severely increased mottled noise/artifacts, which can lead to lowered diagnostic accuracy in clinic. The nonlocal means (NLM) filtering can effectively remove mottled noise/artifacts by utilizing large-scale patch similarity information in LDCT images. But the NLM filtering application in LDCT imaging also requires high computation cost because intensive patch similarity calculation within a large searching window is often required to be used to include enough structure-similarity information for noise/artifact suppression. To improve its clinical feasibility, in this study we further optimize the parallelization of NLM filtering by avoiding the repeated computation with the row-wise intensity calculation and the symmetry weight calculation. The shared memory with fast I/O speed is also used in row-wise intensity calculation for the proposed method. Quantitative experiment demonstrates that significant acceleration can be achieved with respect to the traditional straight pixel-wise parallelization. PMID:26078781

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

    SciTech Connect

    Eck, Brendan L.; Fahmi, Rachid; Miao, Jun; Brown, Kevin M.; Zabic, Stanislav; Raihani, Nilgoun; Wilson, David L.

    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 using 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

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

    PubMed Central

    Eck, Brendan L.; Fahmi, Rachid; Brown, Kevin M.; Zabic, Stanislav; Raihani, Nilgoun; Miao, Jun; Wilson, David L.

    2015-01-01

    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 using 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, PC. 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

  15. Segmentation of the sternum from low-dose chest CT images

    NASA Astrophysics Data System (ADS)

    Liu, Shuang; Xie, Yiting; Reeves, Anthony P.

    2015-03-01

    Segmentation of the sternum in medical images is of clinical significance as it frequently serves as a stable reference to image registration and segmentation of other organs in the chest region. In this paper we present a fully automated algorithm to segment the sternum in low-dose chest CT images (LDCT). The proposed algorithm first locates an axial seed slice and then segments the sternum cross section on the seed slice by matching a rectangle model. Furthermore, it tracks and segments the complete sternum in the cranial and caudal direction respectively through sequential axial slices starting from the seed slice. The cross section on each axial slice is segmented using score functions that are designed to have local maxima at the boundaries of the sternum. Finally, the sternal angle is localized. The algorithm is designed to be specifically robust with respect to cartilage calcifications and to accommodate the high noise levels encountered with LDCT images. Segmentation of 351 cases from public datasets was evaluated visually with only 1 failing to produce a usable segmentation. 87.2% of the 351 images have good segmentation and 12.5% have acceptable segmentation. The sternal body segmentation and the localization of the sternal angle and the vertical extents of the sternum were also evaluated quantitatively for 25 good cases and 25 acceptable cases. The overall weighted mean DC of 0.897 and weighted mean distance error of 2.88 mm demonstrate that the algorithm achieves encouraging performance in both segmenting the sternal body and localizing the sternal angle.

  16. A decrease in lung cancer mortality following the introduction of low-dose chest CT screening in Hitachi, Japan.

    PubMed

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Kusano, Suzushi; Chonan, Tatsuya; Hayashihara, Kenji; Suito, Tetsushi; Endo, Katsuyuki

    2012-12-01

    Recent US clinical trial demonstrated that CT screening prevents lung cancer death among high risk individuals. However, it remains unclear whether wide implementation of low-dose CT screening for lung cancer can decrease mortality in the community. Among residents in Hitachi City (Japan), where nearly 40% of inhabitants aged 50-69 years were estimated to have participated in the screening at least once from 1998 through 2009, the trend of lung cancer mortality was described in relation to the timing of implementation of the CT screening. Cancer mortality data were obtained from regional cancer registry and standardized mortality ratio (SMR) of lung cancer was calculated for each 5-year period during 1995-2009. In both men and women aged 60 years or older, age-specific lung cancer mortality rates were generally lower during 2005-2009 as compared with those during 1995-2004. For combined men and women aged 50-79 years, SMR was nearly unity prior to or during introductory phase of CT screening and during early period of implementation; however, it was significantly decreased during 2005-2009, well after the implementation of CT screening, with SMR (95% confidence interval) being 0.76 (0.67-0.86). Results suggest that wide implementation of low-dose chest CT screening may decrease lung cancer mortality in the community 4-8 years after introduction of the screening.

  17. Algorithm for x-ray beam hardening and scatter correction in low-dose cone-beam CT: phantom studies

    NASA Astrophysics Data System (ADS)

    Liu, Wenlei; Rong, Junyan; Gao, Peng; Liao, Qimei; Lu, HongBing

    2016-03-01

    X-ray scatter poses a significant limitation to image quality in cone-beam CT (CBCT), as well as beam hardening, resulting in image artifacts, contrast reduction, and lack of CT number accuracy. Meanwhile the x-ray radiation dose is also non-ignorable. Considerable scatter or beam hardening correction methods have been developed, independently, and rarely combined with low-dose CT reconstruction. In this paper, we combine scatter suppression with beam hardening correction for sparse-view CT reconstruction to improve CT image quality and reduce CT radiation. Firstly, scatter was measured, estimated, and removed using measurement-based methods, assuming that signal in the lead blocker shadow is only attributable to x-ray scatter. Secondly, beam hardening was modeled by estimating an equivalent attenuation coefficient at the effective energy, which was integrated into the forward projector of the algebraic reconstruction technique (ART). Finally, the compressed sensing (CS) iterative reconstruction is carried out for sparse-view CT reconstruction to reduce the CT radiation. Preliminary Monte Carlo simulated experiments indicate that with only about 25% of conventional dose, our method reduces the magnitude of cupping artifact by a factor of 6.1, increases the contrast by a factor of 1.4 and the CNR by a factor of 15. The proposed method could provide good reconstructed image from a few view projections, with effective suppression of artifacts caused by scatter and beam hardening, as well as reducing the radiation dose. With this proposed framework and modeling, it may provide a new way for low-dose CT imaging.

  18. Automatic lobar segmentation for diseased lungs using an anatomy-based priority knowledge in low-dose CT images

    NASA Astrophysics Data System (ADS)

    Park, Sang Joon; Kim, Jung Im; Goo, Jin Mo; Lee, Doohee

    2014-03-01

    Lung lobar segmentation in CT images is a challenging tasks because of the limitations in image quality inherent to CT image acquisition, especially low-dose CT for clinical routine environment. Besides, complex anatomy and abnormal lesions in the lung parenchyma makes segmentation difficult because contrast in CT images are determined by the differential absorption of X-rays by neighboring structures, such as tissue, vessel or several pathological conditions. Thus, we attempted to develop a robust segmentation technique for normal and diseased lung parenchyma. The images were obtained with low-dose chest CT using soft reconstruction kernel (Sensation 16, Siemens, Germany). Our PC-based in-house software segmented bronchial trees and lungs with intensity adaptive region-growing technique. Then the horizontal and oblique fissures were detected by using eigenvalues-ratio of the Hessian matrix in the lung regions which were excluded from airways and vessels. To enhance and recover the faithful 3-D fissure plane, our proposed fissure enhancing scheme were applied to the images. After finishing above steps, for careful smoothening of fissure planes, 3-D rolling-ball algorithm in xyz planes were performed. Results show that success rate of our proposed scheme was achieved up to 89.5% in the diseased lung parenchyma.

  19. A computer simulation method for low-dose CT images by use of real high-dose images: a phantom study.

    PubMed

    Takenaga, Tomomi; Katsuragawa, Shigehiko; Goto, Makoto; Hatemura, Masahiro; Uchiyama, Yoshikazu; Shiraishi, Junji

    2016-01-01

    Practical simulations of low-dose CT images have a possibility of being helpful means for optimization of the CT exposure dose. Because current methods reported by several researchers are limited to specific vendor platforms and generally rely on raw sinogram data that are difficult to access, we have developed a new computerized scheme for producing simulated low-dose CT images from real high-dose images without use of raw sinogram data or of a particular phantom. Our computerized scheme for low-dose CT simulation was based on the addition of a simulated noise image to a real high-dose CT image reconstructed by the filtered back-projection algorithm. First, a sinogram was generated from the forward projection of a high-dose CT image. Then, an additional noise sinogram resulting from use of a reduced exposure dose was estimated from a predetermined noise model. Finally, a noise CT image was reconstructed with a predetermined filter and was added to the real high-dose CT image to create a simulated low-dose CT image. The noise power spectrum and modulation transfer function of the simulated low-dose images were very close to those of the real low-dose images. In order to confirm the feasibility of our method, we applied this method to clinical cases which were examined with the high dose initially and then followed with a low-dose CT. In conclusion, our proposed method could simulate the low-dose CT images from their real high-dose images with sufficient accuracy and could be used for determining the optimal dose setting for various clinical CT examinations.

  20. Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

    PubMed Central

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  1. A clinical evaluation of total variation-Stokes image reconstruction strategy for low-dose CT imaging of the chest

    NASA Astrophysics Data System (ADS)

    Liu, Yan; Zhang, Hao; Moore, William; Bhattacharji, Priya; Liang, Zhengrong

    2015-03-01

    One hundred "normal-dose" computed tomography (CT) studies of the chest (i.e., 1,160 projection views, 120kVp, 100mAs) data sets were acquired from the patients who were scheduled for lung biopsy at Stony Brook University Hospital under informed consent approved by our Institutional Review Board. To mimic low-dose CT imaging scenario (i.e., sparse-view scan), sparse projection views were evenly extracted from the total 1,160 projections of each patient and the total radiation dose was reduced according to how many sparse views were selected. A standard filtered backprojection (FBP) algorithm was applied to the 1160 projections to produce reference images for comparison purpose. In the low-dose scenario, both the FBP and total variation-stokes (TVS) algorithms were applied to reconstruct the corresponding low-dose images. The reconstructed images were evaluated by an experienced thoracic radiologist against the reference images. Both the low-dose reconstructions and the reference images were displayed on a 4- megapixel monitor in soft tissue and lung windows. The images were graded by a five-point scale from 0 to 4 (0, nondiagnostic; 1, severe artifact with low confidence; 2, moderate artifact or moderate diagnostic confidences; 3, mild artifact or high confidence; 4, well depicted without artifacts). Quantitative evaluation measurements such as standard deviations for different tissue types and universal quality index were also studied and reported for the results. The evaluation concluded that the TVS can reduce the view number from 1,160 to 580 with slightly lower scores as the reference, resulting in a dose reduction to close 50%.

  2. SU-E-I-25: Determining Tube Current, Tube Voltage and Pitch Suitable for Low- Dose Lung Screening CT

    SciTech Connect

    Williams, K; Matthews, K

    2014-06-01

    Purpose: The quality of a computed tomography (CT) image and the dose delivered during its acquisition depend upon the acquisition parameters used. Tube current, tube voltage, and pitch are acquisition parameters that potentially affect image quality and dose. This study investigated physicians' abilities to characterize small, solid nodules in low-dose CT images for combinations of current, voltage and pitch, for three CT scanner models. Methods: Lung CT images was acquired of a Data Spectrum anthropomorphic torso phantom with various combinations of pitch, tube current, and tube voltage; this phantom was used because acrylic beads of various sizes could be placed within the lung compartments to simulate nodules. The phantom was imaged on two 16-slice scanners and a 64-slice scanner. The acquisition parameters spanned a range of estimated CTDI levels; the CTDI estimates from the acquisition software were verified by measurement. Several experienced radiologists viewed the phantom lung CT images and noted nodule location, size and shape, as well as the acceptability of overall image quality. Results: Image quality for assessment of nodules was deemed unsatisfactory for all scanners at 80 kV (any tube current) and at 35 mA (any tube voltage). Tube current of 50 mA or more at 120 kV resulted in similar assessments from all three scanners. Physician-measured sphere diameters were closer to actual diameters for larger spheres, higher tube current, and higher kV. Pitch influenced size measurements less for larger spheres than for smaller spheres. CTDI was typically overestimated by the scanner software compared to measurement. Conclusion: Based on this survey of acquisition parameters, a low-dose CT protocol of 120 kV, 50 mA, and pitch of 1.4 is recommended to balance patient dose and acceptable image quality. For three models of scanners, this protocol resulted in estimated CTDIs from 2.9–3.6 mGy.

  3. Deep convolutional neural networks for automatic coronary calcium scoring in a screening study with low-dose chest CT

    NASA Astrophysics Data System (ADS)

    Lessmann, Nikolas; Išgum, Ivana; Setio, Arnaud A. A.; de Vos, Bob D.; Ciompi, Francesco; de Jong, Pim A.; Oudkerk, Matthjis; Mali, Willem P. Th. M.; Viergever, Max A.; van Ginneken, Bram

    2016-03-01

    The amount of calcifications in the coronary arteries is a powerful and independent predictor of cardiovascular events and is used to identify subjects at high risk who might benefit from preventive treatment. Routine quantification of coronary calcium scores can complement screening programs using low-dose chest CT, such as lung cancer screening. We present a system for automatic coronary calcium scoring based on deep convolutional neural networks (CNNs). The system uses three independently trained CNNs to estimate a bounding box around the heart. In this region of interest, connected components above 130 HU are considered candidates for coronary artery calcifications. To separate them from other high intensity lesions, classification of all extracted voxels is performed by feeding two-dimensional 50 mm × 50 mm patches from three orthogonal planes into three concurrent CNNs. The networks consist of three convolutional layers and one fully-connected layer with 256 neurons. In the experiments, 1028 non-contrast-enhanced and non-ECG-triggered low-dose chest CT scans were used. The network was trained on 797 scans. In the remaining 231 test scans, the method detected on average 194.3 mm3 of 199.8 mm3 coronary calcifications per scan (sensitivity 97.2 %) with an average false-positive volume of 10.3 mm3 . Subjects were assigned to one of five standard cardiovascular risk categories based on the Agatston score. Accuracy of risk category assignment was 84.4 % with a linearly weighted κ of 0.89. The proposed system can perform automatic coronary artery calcium scoring to identify subjects undergoing low-dose chest CT screening who are at risk of cardiovascular events with high accuracy.

  4. The evidence for low-dose CT screening of lung cancer.

    PubMed

    Ruchalski, Kathleen; Gutierrez, Antonio; Genshaft, Scott; Abtin, Fereidoun; Suh, Robert

    2016-01-01

    Lung cancer remains the leading cause of cancer-related death in the United States. An effective screening tool for early lung cancer detection has long been sought. Early chest radiograph and low-dose computed tomography (LDCT) screening trials were promising and demonstrated increased cancer detection. However, these studies were not able to improve lung cancer mortality. The National Lung Screening Trial resulted in decreased lung cancer mortality with LDCT screening in a high-risk population. Similar trials are currently underway in Europe. With LDCT now being widely implemented, it is paramount for radiologists to understand the evidence for lung cancer screening.

  5. Ultra-low dose comprehensive cardiac CT imaging in a patient with acute myocarditis.

    PubMed

    Tröbs, Monique; Brand, Michael; Achenbach, Stephan; Marwan, Mohamed

    2014-01-01

    The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been previously reported. We report a case of acute myocarditis with coronary CT angiography as well as "late enhancement" imaging with ultra-low effective radiation dose. PMID:25439792

  6. Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas

    PubMed Central

    Sabaté-Llobera, Aida; Cortés-Romera, Montserrat; Mercadal, Santiago; Hernández-Gañán, Javier; Pomares, Helena; González-Barca, Eva; Gámez-Cenzano, Cristina

    2016-01-01

    Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary. PMID:27559300

  7. Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas.

    PubMed

    Sabaté-Llobera, Aida; Cortés-Romera, Montserrat; Mercadal, Santiago; Hernández-Gañán, Javier; Pomares, Helena; González-Barca, Eva; Gámez-Cenzano, Cristina

    2016-01-01

    Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-((18)F)fluoro-d-glucose ((18)F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary.

  8. Adaptive multi-scale total variation minimization filter for low dose CT imaging

    NASA Astrophysics Data System (ADS)

    Zamyatin, Alexander; Katsevich, Gene; Krylov, Roman; Shi, Bibo; Yang, Zhi

    2014-03-01

    In this work we revisit TV filter and propose an improved version that is tailored to diagnostic CT purposes. We revise TV cost function, which results in symmetric gradient function that leads to more natural noise texture. We apply a multi-scale approach to resolve noise grain issue in CT images. We examine noise texture, granularity, and loss of low contrast in the test images. We also discuss potential acceleration by Nesterov and Conjugate Gradient methods.

  9. Accuracy and Precision of Three-Dimensional Low Dose CT Compared to Standard RSA in Acetabular Cups: An Experimental Study

    PubMed Central

    Olivecrona, Henrik; Maguire, Gerald Q.; Noz, Marilyn E.; Zeleznik, Michael P.

    2016-01-01

    Background and Purpose. The gold standard for detection of implant wear and migration is currently radiostereometry (RSA). The purpose of this study is to compare a three-dimensional computed tomography technique (3D CT) to standard RSA as an alternative technique for measuring migration of acetabular cups in total hip arthroplasty. Materials and Methods. With tantalum beads, we marked one cemented and one uncemented cup and mounted these on a similarly marked pelvic model. A comparison was made between 3D CT and standard RSA for measuring migration. Twelve repeated stereoradiographs and CT scans with double examinations in each position and gradual migration of the implants were made. Precision and accuracy of the 3D CT were calculated. Results. The accuracy of the 3D CT ranged between 0.07 and 0.32 mm for translations and 0.21 and 0.82° for rotation. The precision ranged between 0.01 and 0.09 mm for translations and 0.06 and 0.29° for rotations, respectively. For standard RSA, the precision ranged between 0.04 and 0.09 mm for translations and 0.08 and 0.32° for rotations, respectively. There was no significant difference in precision between 3D CT and standard RSA. The effective radiation dose of the 3D CT method, comparable to RSA, was estimated to be 0.33 mSv. Interpretation. Low dose 3D CT is a comparable method to standard RSA in an experimental setting. PMID:27478832

  10. Accuracy and Precision of Three-Dimensional Low Dose CT Compared to Standard RSA in Acetabular Cups: An Experimental Study.

    PubMed

    Brodén, Cyrus; Olivecrona, Henrik; Maguire, Gerald Q; Noz, Marilyn E; Zeleznik, Michael P; Sköldenberg, Olof

    2016-01-01

    Background and Purpose. The gold standard for detection of implant wear and migration is currently radiostereometry (RSA). The purpose of this study is to compare a three-dimensional computed tomography technique (3D CT) to standard RSA as an alternative technique for measuring migration of acetabular cups in total hip arthroplasty. Materials and Methods. With tantalum beads, we marked one cemented and one uncemented cup and mounted these on a similarly marked pelvic model. A comparison was made between 3D CT and standard RSA for measuring migration. Twelve repeated stereoradiographs and CT scans with double examinations in each position and gradual migration of the implants were made. Precision and accuracy of the 3D CT were calculated. Results. The accuracy of the 3D CT ranged between 0.07 and 0.32 mm for translations and 0.21 and 0.82° for rotation. The precision ranged between 0.01 and 0.09 mm for translations and 0.06 and 0.29° for rotations, respectively. For standard RSA, the precision ranged between 0.04 and 0.09 mm for translations and 0.08 and 0.32° for rotations, respectively. There was no significant difference in precision between 3D CT and standard RSA. The effective radiation dose of the 3D CT method, comparable to RSA, was estimated to be 0.33 mSv. Interpretation. Low dose 3D CT is a comparable method to standard RSA in an experimental setting. PMID:27478832

  11. Adaptive nonlocal means-based regularization for statistical image reconstruction of low-dose X-ray CT

    NASA Astrophysics Data System (ADS)

    Zhang, Hao; Ma, Jianhua; Wang, Jing; Liu, Yan; Han, Hao; Li, Lihong; Moore, William; Liang, Zhengrong

    2015-03-01

    To reduce radiation dose in X-ray computed tomography (CT) imaging, one of the common strategies is to lower the milliampere-second (mAs) setting during projection data acquisition. However, this strategy would inevitably increase the projection data noise, and the resulting image by the filtered back-projection (FBP) method may suffer from excessive noise and streak artifacts. The edge-preserving nonlocal means (NLM) filtering can help to reduce the noise-induced artifacts in the FBP reconstructed image, but it sometimes cannot completely eliminate them, especially under very low-dose circumstance when the image is severely degraded. To deal with this situation, we proposed a statistical image reconstruction scheme using a NLM-based regularization, which can suppress the noise and streak artifacts more effectively. However, we noticed that using uniform filtering parameter in the NLM-based regularization was rarely optimal for the entire image. Therefore, in this study, we further developed a novel approach for designing adaptive filtering parameters by considering local characteristics of the image, and the resulting regularization is referred to as adaptive NLM-based regularization. Experimental results with physical phantom and clinical patient data validated the superiority of using the proposed adaptive NLM-regularized statistical image reconstruction method for low-dose X-ray CT, in terms of noise/streak artifacts suppression and edge/detail/contrast/texture preservation.

  12. Comparison of biophysical factors influencing on emphysema quantification with low-dose CT

    NASA Astrophysics Data System (ADS)

    Heo, Chang Yong; Kim, Jong Hyo

    2014-03-01

    Emphysema Index(EI) measurements in MDCT is known to be influenced by various biophysical factors such as total lung volume, and body size. We investigated the association of the four biophysical factors with emphysema index in low-dose MDCT. In particular, we attempted to identify a potentially stronger biophysical factor than total lung volume. A total of 400 low-dose MDCT volumes taken at 120kVp, 40mAs, 1mm thickness, and B30f reconstruction kernel were used. The lungs, airways, and pulmonary vessels were automatically segmented, and two Emphysema Indices, relative area below -950HU(RA950) and 15th percentile(Perc15), were extracted from the segmented lungs. The biophysical factors such as total lung volume(TLV), mode of lung attenuation(ModLA), effective body diameter(EBD), and the water equivalent body diameter(WBD) were estimated from the segmented lung and body area. The association of biophysical factors with emphysema indices were evaluated by correlation coefficients. The mean emphysema indices were 8.3±5.5(%) in RA950, and -930±18(HU) in Perc15. The estimates of biophysical factors were 4.7±1.0(L) in TLV, -901±21(HU) in ModLA, 26.9±2.2(cm) in EBD, and 25.9±2.6(cm) in WBD. The correlation coefficients of biophysical factors with RA950 were 0.73 in TLV, 0.94 in ModLA, 0.31 in EBD, and 0.18 WBD, the ones with Perc15 were 0.74 in TLV, 0.98 in ModLA, 0.29 in EBD, and 0.15 WBD. Study results revealed that two biophysical factors, TLV and ModLA, mostly affects the emphysema indices. In particular, the ModLA exhibited strongest correlation of 0.98 with Perc15, which indicating the ModLA is the most significant confounding biophysical factor in emphysema indices measurement.

  13. Low-dose megavoltage cone-beam CT imaging using thick, segmented scintillators

    NASA Astrophysics Data System (ADS)

    El-Mohri, Youcef; Antonuk, Larry E.; Zhao, Qihua; Choroszucha, Richard B.; Jiang, Hao; Liu, Langechuan

    2011-03-01

    Megavoltage, cone-beam computed tomography (MV CBCT) employing an electronic portal imaging device (EPID) is a highly promising technique for providing soft-tissue visualization in image-guided radiotherapy. However, current EPIDs based on active matrix flat-panel imagers (AMFPIs), which are regarded as the gold standard for portal imaging and referred to as conventional MV AMFPIs, require high radiation doses to achieve this goal due to poor x-ray detection efficiency (~2% at 6 MV). To overcome this limitation, the incorporation of thick, segmented, crystalline scintillators, as a replacement for the phosphor screens used in these AMFPIs, has been shown to significantly improve the detective quantum efficiency (DQE) performance, leading to improved image quality for projection imaging at low dose. Toward the realization of practical AMFPIs capable of low dose, soft-tissue visualization using MV CBCT imaging, two prototype AMFPIs incorporating segmented scintillators with ~11 mm thick CsI:Tl and Bi4Ge3O12 (BGO) crystals were evaluated. Each scintillator consists of 120 × 60 crystalline elements separated by reflective septal walls, with an element-to-element pitch of 1.016 mm. The prototypes were evaluated using a bench-top CBCT system, allowing the acquisition of 180 projection, 360° tomographic scans with a 6 MV radiotherapy photon beam. Reconstructed images of a spatial resolution phantom, as well as of a water-equivalent phantom, embedded with tissue equivalent objects having electron densities (relative to water) varying from ~0.28 to ~1.70, were obtained down to one beam pulse per projection image, corresponding to a scan dose of ~4 cGy--a dose similar to that required for a single portal image obtained from a conventional MV AMFPI. By virtue of their significantly improved DQE, the prototypes provided low contrast visualization, allowing clear delineation of an object with an electron density difference of ~2.76%. Results of contrast, noise and contrast

  14. 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.

  15. The assessment of the role of baseline low-dose CT scan in patients at high risk of lung cancer

    PubMed Central

    Kołaczyk, Katarzyna; Walecka, Anna; Grodzki, Tomasz; Alchimowicz, Jacek; Smereczyński, Andrzej; Kiedrowicz, Radosław

    2014-01-01

    Summary Background Despite the progress in contemporary medicine comprising diagnostic and therapeutic methods, lung cancer is still one of the biggest health concerns in many countries of the world. The main purpose of the study was to evaluate the detection rate of pulmonary nodules and lung cancer in the initial, helical low-dose CT of the chest as well as the analysis of the relationship between the size and the histopathological character of the detected nodules. Material/Methods We retrospectively evaluated 1999 initial, consecutive results of the CT examinations performed within the framework of early lung cancer detection program initiated in Szczecin. The project enrolled persons of both sexes, aged 55–65 years, with at least 20 pack-years of cigarette smoking or current smokers. The analysis included assessment of the number of positive results and the evaluation of the detected nodules in relationship to their size. All of the nodules were classified into I of VI groups and subsequently compared with histopathological type of the neoplastic and nonneoplastic pulmonary lesions. Results Pulmonary nodules were detected in 921 (46%) subjects. What is more, malignant lesions as well as lung cancer were significantly, more frequently discovered in the group of asymptomatic nodules of the largest dimension exceeding 15 mm. Conclusions The initial, low-dose helical CT of the lungs performed in high risk individuals enables detection of appreciable number of indeterminate pulmonary nodules. In most of the asymptomatic patients with histopathologically proven pulmonary nodules greater than 15 mm, the mentioned lesions are malignant, what warrants further, intensified diagnostics. PMID:25057333

  16. Automatic LV volume measurement in low dose multi-phase CT by shape tracking

    NASA Astrophysics Data System (ADS)

    von Berg, Jens; Begemann, Philipp; Stahmer, Felix; Adam, Gerhard; Lorenz, Cristian

    2006-03-01

    Functional assessment of cardiac ventricular function requires time consuming manual interaction. Some automated methods have been presented that predominantly used cardiac magnet resonance images. Here, an automatic shape tracking approach is followed to estimate left ventricular blood volume from multi-slice computed tomography image series acquired with retrospective ECG-gating. A deformable surface model method was chosen that utilized both shape and local appearance priors to determine the endocardial surface and to follow its motion through the cardiac cycle. Functional parameters like the ejection fraction could be calculated from the estimated shape deformation. A clinical validation was performed in a porcine model with 60 examinations on eight subjects. The functional parameters showed a good correlation with those determined by clinical experts using a commercially available semi-automatic short axes delineation tool. The correlation coefficient for the ejection fraction (EF) was 0.89. One quarter of these acquisitions were done with a low dose protocol. All of these degraded images could be processed well. Their correlation slightly decreases when compared to the normal dose cases (EF: 0.87 versus 0.88).

  17. Investigating the low-dose limits of multidetector CT in lung nodule surveillance.

    PubMed

    Paul, N S; Siewerdsen, J H; Patsios, D; Chung, T B

    2007-09-01

    The purpose of this study was to evaluate the factors limiting nodule detection in thoracic computed tomography (CT) and to determine whether prior knowledge of nodule size and attenuation, available from a baseline CT study, influences the minimum radiation dose at which nodule surveillance CT scans can be performed while maintaining current levels of nodule detectability. Multiple nodules varying in attenuation (-509 to + 110 HU) and diameter (1.6 to 9.5 mm) were layered in random and ordered sequences within 2 lung cylinders made of Rando lung material and suspended within a custom-built CT phantom. Multiple CT scans were performed at varying kVp (120, 100, and 80), mA (200, 150, 100, 50, 20, and 10), and beam collimation (5, 2.5, and 1.25 mm) on a four-row multidetector scanner (Lightspeed, General Electric, Milwaukee, WI) using 0.8 s gantry rotation. The corresponding range of radiation dose over which images were acquired was 0.3-26.4 mGy. Nine observers independently performed three specific tasks, namely: (1) To detect a 3.2 mm nodule of 23 HU; (2) To detect 3.2 mm nodules of varying attenuation (-509 to -154 HU); and (3) To detect nodules varying in size (1.6-9 mm) and attenuation (-509 to 110 HU). A two-alternative forced-choice test was used in order to determine the limits of nodule detection in terms of the proportion of correct responses (Pcorr, related to the area under the ROC curve) as a summary metric of observer performance. The radiation dose levels for detection of 99% of nodules in each task were as follows: Task 1 (1 mGy); Task 2 (5 mGy); and Task 3 (7 mGy). The corresponding interobserver confidence limits were 1, 5, and 10 mGy for Tasks 1, 2, and 3, respectively. There was a fivefold increase in the radiation dose required for detection of lower-density nodules (Tasks 1 to 2). Absence of prior knowledge of the nodule size and density (Task 3) corresponds to a significant increase in the minimum required radiation dose. Significant image

  18. Projection domain denoising method based on dictionary learning for low-dose CT image reconstruction.

    PubMed

    Zhang, Haiyan; Zhang, Liyi; Sun, Yunshan; Zhang, Jingyu

    2015-01-01

    Reducing X-ray tube current is one of the widely used methods for decreasing the radiation dose. Unfortunately, the signal-to-noise ratio (SNR) of the projection data degrades simultaneously. To improve the quality of reconstructed images, a dictionary learning based penalized weighted least-squares (PWLS) approach is proposed for sinogram denoising. The weighted least-squares considers the statistical characteristic of noise and the penalty models the sparsity of sinogram based on dictionary learning. Then reconstruct CT image using filtered back projection (FBP) algorithm from the denoised sinogram. The proposed method is particularly suitable for the projection data with low SNR. Experimental results show that the proposed method can get high-quality CT images when the signal to noise ratio of projection data declines sharply.

  19. Low-Dose CT Screening for Lung Cancer: Computer-aided Detection of Missed Lung Cancers.

    PubMed

    Liang, Mingzhu; Tang, Wei; Xu, Dong Ming; Jirapatnakul, Artit C; Reeves, Anthony P; Henschke, Claudia I; Yankelevitz, David

    2016-10-01

    Purpose To update information regarding the usefulness of computer-aided detection (CAD) systems with a focus on the most critical category, that of missed cancers at earlier imaging, for cancers that manifest as a solid nodule. Materials and Methods By using a HIPAA-compliant institutional review board-approved protocol where informed consent was obtained, 50 lung cancers that manifested as a solid nodule on computed tomographic (CT) scans in annual rounds of screening (time 1) were retrospectively identified that could, in retrospect, be identified on the previous CT scans (time 0). Four CAD systems were compared, which were referred to as CAD 1, CAD 2, CAD 3, and CAD 4. The total number of accepted CAD-system-detected nodules at time 0 was determined by consensus of two radiologists and the number of CAD-system-detected nodules that were rejected by the radiologists was also documented. Results At time 0 when all the cancers had been missed, CAD system detection rates for the cancers were 56%, 70%, 68%, and 60% (κ = 0.45) for CAD systems 1, 2, 3, and 4, respectively. At time 1, the rates were 74%, 82%, 82%, and 78% (κ = 0.32), respectively. The average diameter of the 50 cancers at time 0 and time 1 was 4.8 mm and 11.4 mm, respectively. The number of CAD-system-detected nodules that were rejected per CT scan for CAD systems 1-4 at time 0 was 7.4, 1.7, 0.6, and 4.5 respectively. Conclusion CAD systems detected up to 70% of lung cancers that were not detected by the radiologist but failed to detect about 20% of the lung cancers when they were identified by the radiologist, which suggests that CAD may be useful in the role of second reader. (©) RSNA, 2016.

  20. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  1. Low-Dose Micro-CT Imaging for Vascular Segmentation and Analysis Using Sparse-View Acquisitions

    PubMed Central

    Vandeghinste, Bert; Vandenberghe, Stefaan; Vanhove, Chris; Staelens, Steven; Van Holen, Roel

    2013-01-01

    The aim of this study is to investigate whether reliable and accurate 3D geometrical models of the murine aortic arch can be constructed from sparse-view data in vivo micro-CT acquisitions. This would considerably reduce acquisition time and X-ray dose. In vivo contrast-enhanced micro-CT datasets were reconstructed using a conventional filtered back projection algorithm (FDK), the image space reconstruction algorithm (ISRA) and total variation regularized ISRA (ISRA-TV). The reconstructed images were then semi-automatically segmented. Segmentations of high- and low-dose protocols were compared and evaluated based on voxel classification, 3D model diameters and centerline differences. FDK reconstruction does not lead to accurate segmentation in the case of low-view acquisitions. ISRA manages accurate segmentation with 1024 or more projection views. ISRA-TV needs a minimum of 256 views. These results indicate that accurate vascular models can be obtained from micro-CT scans with 8 times less X-ray dose and acquisition time, as long as regularized iterative reconstruction is used. PMID:23840893

  2. Low dose CT image restoration using a database of image patches

    NASA Astrophysics Data System (ADS)

    Ha, Sungsoo; Mueller, Klaus

    2015-01-01

    Reducing the radiation dose in CT imaging has become an active research topic and many solutions have been proposed to remove the significant noise and streak artifacts in the reconstructed images. Most of these methods operate within the domain of the image that is subject to restoration. This, however, poses limitations on the extent of filtering possible. We advocate to take into consideration the vast body of external knowledge that exists in the domain of already acquired medical CT images, since after all, this is what radiologists do when they examine these low quality images. We can incorporate this knowledge by creating a database of prior scans, either of the same patient or a diverse corpus of different patients, to assist in the restoration process. Our paper follows up on our previous work that used a database of images. Using images, however, is challenging since it requires tedious and error prone registration and alignment. Our new method eliminates these problems by storing a diverse set of small image patches in conjunction with a localized similarity matching scheme. We also empirically show that it is sufficient to store these patches without anatomical tags since their statistics are sufficiently strong to yield good similarity matches from the database and as a direct effect, produce image restorations of high quality. A final experiment demonstrates that our global database approach can recover image features that are difficult to preserve with conventional denoising approaches.

  3. Extracting Information From Previous Full-Dose CT Scan for Knowledge-Based Bayesian Reconstruction of Current Low-Dose CT Images.

    PubMed

    Zhang, Hao; Han, Hao; Liang, Zhengrong; Hu, Yifan; Liu, Yan; Moore, William; Ma, Jianhua; Lu, Hongbing

    2016-03-01

    Markov random field (MRF) model has been widely employed in edge-preserving regional noise smoothing penalty to reconstruct piece-wise smooth images in the presence of noise, such as in low-dose computed tomography (LdCT). While it preserves edge sharpness, its regional smoothing may sacrifice tissue image textures, which have been recognized as useful imaging biomarkers, and thus it may compromise clinical tasks such as differentiating malignant vs. benign lesions, e.g., lung nodules or colon polyps. This study aims to shift the edge-preserving regional noise smoothing paradigm to texture-preserving framework for LdCT image reconstruction while retaining the advantage of MRF's neighborhood system on edge preservation. Specifically, we adapted the MRF model to incorporate the image textures of muscle, fat, bone, lung, etc. from previous full-dose CT (FdCT) scan as a priori knowledge for texture-preserving Bayesian reconstruction of current LdCT images. To show the feasibility of the proposed reconstruction framework, experiments using clinical patient scans were conducted. The experimental outcomes showed a dramatic gain by the a priori knowledge for LdCT image reconstruction using the commonly-used Haralick texture measures. Thus, it is conjectured that the texture-preserving LdCT reconstruction has advantages over the edge-preserving regional smoothing paradigm for texture-specific clinical applications.

  4. Robust Low-dose CT Perfusion Deconvolution via Tensor Total-Variation Regularization

    PubMed Central

    Zhang, Shaoting; Chen, Tsuhan; Sanelli, Pina C.

    2016-01-01

    Acute brain diseases such as acute strokes and transit ischemic attacks are the leading causes of mortality and morbidity worldwide, responsible for 9% of total death every year. ‘Time is brain’ is a widely accepted concept in acute cerebrovascular disease treatment. Efficient and accurate computational framework for hemodynamic parameters estimation can save critical time for thrombolytic therapy. Meanwhile the high level of accumulated radiation dosage due to continuous image acquisition in CT perfusion (CTP) raised concerns on patient safety and public health. However, low-radiation leads to increased noise and artifacts which require more sophisticated and time-consuming algorithms for robust estimation. In this paper, we focus on developing a robust and efficient framework to accurately estimate the perfusion parameters at low radiation dosage. Specifically, we present a tensor total-variation (TTV) technique which fuses the spatial correlation of the vascular structure and the temporal continuation of the blood signal flow. An efficient algorithm is proposed to find the solution with fast convergence and reduced computational complexity. Extensive evaluations are carried out in terms of sensitivity to noise levels, estimation accuracy, contrast preservation, and performed on digital perfusion phantom estimation, as well as in-vivo clinical subjects. Our framework reduces the necessary radiation dose to only 8% of the original level and outperforms the state-of-art algorithms with peak signal-to-noise ratio improved by 32%. It reduces the oscillation in the residue functions, corrects over-estimation of cerebral blood flow (CBF) and under-estimation of mean transit time (MTT), and maintains the distinction between the deficit and normal regions. PMID:25706579

  5. Fast radioactive seed localization in intraoperative cone beam CT for low-dose-rate prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Hu, Yu-chi; Xiong, Jian-ping; Cohan, Gilad; Zaider, Marco; Mageras, Gig; Zelefsky, Michael

    2013-03-01

    A fast knowledge-based radioactive seed localization method for brachytherapy was developed to automatically localize radioactive seeds in an intraoperative volumetric cone beam CT (CBCT) so that corrections, if needed, can be made during prostate implant surgery. A transrectal ultrasound (TRUS) scan is acquired for intraoperative treatment planning. Planned seed positions are transferred to intraoperative CBCT following TRUS-to-CBCT registration using a reference CBCT scan of the TRUS probe as a template, in which the probe and its external fiducial markers are pre-segmented and their positions in TRUS are known. The transferred planned seeds and probe serve as an atlas to reduce the search space in CBCT. Candidate seed voxels are identified based on image intensity. Regions are grown from candidate voxels and overlay regions are merged. Region volume and intensity variance is checked against known seed volume and intensity profile. Regions meeting the above criteria are flagged as detected seeds; otherwise they are flagged as likely seeds and sorted by a score that is based on volume, intensity profile and distance to the closest planned seed. A graphical interface allows users to review and accept or reject likely seeds. Likely seeds with approximately twice the seed volume are automatically split. Five clinical cases are tested. Without any manual correction in seed detection, the method performed the localization in 5 seconds (excluding registration time) for a CBCT scan with 512×512×192 voxels. The average precision rate per case is 99% and the recall rate is 96% for a total of 416 seeds. All false negative seeds are found with 15 in likely seeds and 1 included in a detected seed. With the new method, updating of calculations of dose distribution during the procedure is possible and thus facilitating evaluation and improvement of treatment quality.

  6. Combining Automatic Tube Current Modulation with Adaptive Statistical Iterative Reconstruction for Low-Dose Chest CT Screening

    PubMed Central

    Chen, Jiang-Hong; Jin, Er-Hu; He, Wen; Zhao, Li-Qin

    2014-01-01

    Objective To reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT) by combining adaptive statistical iterative reconstruction (ASIR) and automatic tube current modulation (ATCM). Methods Patients undergoing cancer screening (n = 200) were subjected to 64-slice multidetector chest CT scanning with ASIR and ATCM. Patients were divided into groups 1, 2, 3, and 4 (n = 50 each), with a noise index (NI) of 15, 20, 30, and 40, respectively. Each image set was reconstructed with 4 ASIR levels (0% ASIR, 30% ASIR, 50% ASIR, and 80% ASIR) in each group. Two radiologists assessed subjective image noise, image artifacts, and visibility of the anatomical structures. Objective image noise and signal-to-noise ratio (SNR) were measured, and effective dose (ED) was recorded. Results Increased NI was associated with increased subjective and objective image noise results (P<0.001), and SNR decreased with increasing NI (P<0.001). These values improved with increased ASIR levels (P<0.001). Images from all 4 groups were clinically diagnosable. Images with NI = 30 and 50% ASIR had average subjective image noise scores and nearly average anatomical structure visibility scores, with a mean objective image noise of 23.42 HU. The EDs for groups 1, 2, 3 and 4 were 2.79±1.17, 1.69±0.59, 0.74±0.29, and 0.37±0.22 mSv, respectively. Compared to group 1 (NI = 15), the ED reductions were 39.43%, 73.48%, and 86.74% for groups 2, 3, and 4, respectively. Conclusions Using NI = 30 with 50% ASIR in the chest CT protocol, we obtained average or above-average image quality but a reduced ED. PMID:24691208

  7. NIH-funded study shows 20 percent reduction in lung cancer mortality with low-dose CT compared to chest X-ray: | Division of Cancer Prevention

    Cancer.gov

    Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray. The primary research results from the National Lung Screening Trial (NLST) were published online today in the New England Journal of Medicine. |

  8. Low-dose preview for patient-specific, task-specific technique selection in cone-beam CT

    SciTech Connect

    Wang, Adam S.; Stayman, J. Webster; Otake, Yoshito; Siewerdsen, Jeffrey H.; Vogt, Sebastian; Kleinszig, Gerhard; Khanna, A. Jay; Gallia, Gary L.

    2014-07-15

    Purpose : A method is presented for generating simulated low-dose cone-beam CT (CBCT) preview images from which patient- and task-specific minimum-dose protocols can be confidently selected prospectively in clinical scenarios involving repeat scans. Methods : In clinical scenarios involving a series of CBCT images, the low-dose preview (LDP) method operates upon the first scan to create a projection dataset that accurately simulates the effects of dose reduction in subsequent scans by injecting noise of proper magnitude and correlation, including both quantum and electronic readout noise as important components of image noise in flat-panel detector CBCT. Experiments were conducted to validate the LDP method in both a head phantom and a cadaveric torso by performing CBCT acquisitions spanning a wide dose range (head: 0.8–13.2 mGy, body: 0.8–12.4 mGy) with a prototype mobile C-arm system. After injecting correlated noise to simulate dose reduction, the projections were reconstructed using both conventional filtered backprojection (FBP) and an iterative, model-based image reconstruction method (MBIR). The LDP images were then compared to real CBCT images in terms of noise magnitude, noise-power spectrum (NPS), spatial resolution, contrast, and artifacts. Results : For both FBP and MBIR, the LDP images exhibited accurate levels of spatial resolution and contrast that were unaffected by the correlated noise injection, as expected. Furthermore, the LDP image noise magnitude and NPS were in strong agreement with real CBCT images acquired at the corresponding, reduced dose level across the entire dose range considered. The noise magnitude agreed within 7% for both the head phantom and cadaveric torso, and the NPS showed a similar level of agreement up to the Nyquist frequency. Therefore, the LDP images were highly representative of real image quality across a broad range of dose and reconstruction methods. On the other hand, naïve injection ofuncorrelated noise

  9. Over-exposure correction in knee cone-beam CT imaging with automatic exposure control using a partial low dose scan

    NASA Astrophysics Data System (ADS)

    Choi, Jang-Hwan; Muller, Kerstin; Hsieh, Scott; Maier, Andreas; Gold, Garry; Levenston, Marc; Fahrig, Rebecca

    2016-03-01

    C-arm-based cone-beam CT (CBCT) systems with flat-panel detectors are suitable for diagnostic knee imaging due to their potentially flexible selection of CT trajectories and wide volumetric beam coverage. In knee CT imaging, over-exposure artifacts can occur because of limitations in the dynamic range of the flat panel detectors present on most CBCT systems. We developed a straightforward but effective method for correction and detection of over-exposure for an Automatic Exposure Control (AEC)-enabled standard knee scan incorporating a prior low dose scan. The radiation dose associated with the low dose scan was negligible (0.0042mSv, 2.8% increase) which was enabled by partially sampling the projection images considering the geometry of the knees and lowering the dose further to be able to just see the skin-air interface. We combined the line integrals from the AEC and low dose scans after detecting over-exposed regions by comparing the line profiles of the two scans detector row-wise. The combined line integrals were reconstructed into a volumetric image using filtered back projection. We evaluated our method using in vivo human subject knee data. The proposed method effectively corrected and detected over-exposure, and thus recovered the visibility of exterior tissues (e.g., the shape and density of the patella, and the patellar tendon), incorporating a prior low dose scan with a negligible increase in radiation exposure.

  10. The Head to Head That Had to Happen: A Case Study of Television Sport and Entrepreneurship.

    ERIC Educational Resources Information Center

    Whannel, Garry

    The race between Mary Decker and Zola Budd, a head to head confrontation in the 1985 Olympic Games, is examined within the broader context of the transformation taking place in sports as a result of the combined efforts of television and the economic forces of sponsorship. Athletics is going through this process of transformation both economically…

  11. TU-A-12A-09: Absolute Blood Flow Measurement in a Cardiac Phantom Using Low Dose CT

    SciTech Connect

    Ziemer, B; Hubbard, L; Lipinski, J; Molloi, S

    2014-06-15

    Purpose: To investigate a first pass analysis technique to measure absolute flow from low dose CT images in a cardiac phantom. This technique can be combined with a myocardial mass assignment to yield absolute perfusion using only two volume scans and reduce the radiation dose to the patient. Methods: A four-chamber cardiac phantom and perfusion chamber were constructed from poly-acrylic and connected with tubing to approximate anatomical features. The system was connected to a pulsatile pump, input/output reservoirs and power contrast injector. Flow was varied in the range of 1-2.67 mL/s with the pump operating at 60 beats/min. The system was imaged once a second for 14 seconds with a 320-row scanner (Toshiba Medical Systems) using a contrast-enhanced, prospective-gated cardiac perfusion protocol. Flow was calculated by the following steps: subsequent images of the perfusion volume were subtracted to find the contrast entering the volume; this was normalized by an upstream, known volume region to convert Hounsfield (HU) values to concentration; this was divided by the subtracted images time difference. The technique requires a relatively stable input contrast concentration and no contrast can leave the perfusion volume before the flow measurement is completed. Results: The flow calculated from the images showed an excellent correlation with the known rates. The data was fit to a linear function with slope 1.03, intercept 0.02 and an R{sup 2} value of 0.99. The average root mean square (RMS) error was 0.15 mL/s and the average standard deviation was 0.14 mL/s. The flow rate was stable within 7.7% across the full scan and served to validate model assumptions. Conclusion: Accurate, absolute flow rates were measured from CT images using a conservation of mass model. Measurements can be made using two volume scans which can substantially reduce the radiation dose compared with current dynamic perfusion techniques.

  12. Texture-preserved penalized weighted least-squares reconstruction of low-dose CT image via image segmentation and high-order MRF modeling

    NASA Astrophysics Data System (ADS)

    Han, Hao; Zhang, Hao; Wei, Xinzhou; Moore, William; Liang, Zhengrong

    2016-03-01

    In this paper, we proposed a low-dose computed tomography (LdCT) image reconstruction method with the help of prior knowledge learning from previous high-quality or normal-dose CT (NdCT) scans. The well-established statistical penalized weighted least squares (PWLS) algorithm was adopted for image reconstruction, where the penalty term was formulated by a texture-based Gaussian Markov random field (gMRF) model. The NdCT scan was firstly segmented into different tissue types by a feature vector quantization (FVQ) approach. Then for each tissue type, a set of tissue-specific coefficients for the gMRF penalty was statistically learnt from the NdCT image via multiple-linear regression analysis. We also proposed a scheme to adaptively select the order of gMRF model for coefficients prediction. The tissue-specific gMRF patterns learnt from the NdCT image were finally used to form an adaptive MRF penalty for the PWLS reconstruction of LdCT image. The proposed texture-adaptive PWLS image reconstruction algorithm was shown to be more effective to preserve image textures than the conventional PWLS image reconstruction algorithm, and we further demonstrated the gain of high-order MRF modeling for texture-preserved LdCT PWLS image reconstruction.

  13. SU-E-I-86: Ultra-Low Dose Computed Tomography Attenuation Correction for Pediatric PET CT Using Adaptive Statistical Iterative Reconstruction (ASiR™)

    SciTech Connect

    Brady, S; Shulkin, B

    2015-06-15

    Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co

  14. Low-dose CT imaging of radio-opaque markers for assessing human rotator cuff repair: accuracy, repeatability and the effect of arm position.

    PubMed

    Derwin, K A; Milks, R A; Davidson, I; Iannotti, J P; McCarron, J A; Bey, M J

    2012-02-01

    Previous studies have used radiostereometric analysis (RSA) to assess the integrity and mechanical properties of repaired tendons and ligament grafts. A conceptually similar approach is to use CT imaging to measure the 3D position and distance between implanted markers. The purpose of this study was to quantify the accuracy and repeatability of measuring the position and distance between metallic markers placed in the rotator cuff using low-dose CT imaging. We also investigated the effect of repeated or variable positions of the arm on position and distance measures. Six human patients had undergone rotator cuff repair and placement of tantalum beads in the rotator cuff at least one year prior to participating in this study. On a single day each patient underwent nine low-dose CT scans in seven unique arm positions. CT scans were analyzed to assess bias, precision and RMS error of the measurement technique. The effect of repeated or variable positions of the arm on the 3D position of the beads and the distance between these beads and suture anchors in the humeral head were also assessed. Results showed the CT imaging method is accurate and repeatable to within 0.7 mm. Further, measures of bead position and anchor-to-bead distance are influenced by arm position and location of the bead within the rotator cuff. Beads located in the posterior rotator cuff moved medially as much as 20 mm in abduction or external rotation. When clinically relevant CT arm positions such as the hand on umbilicus or at side were repeated, bead position varied less than 4 mm in any anatomic direction and anchor-to-bead distance varied +2.8 to -1.6 mm (RMS 1.3 mm). We conclude that a range of ± 3 mm is a conservative estimate of the uncertainty in anchor-to-bead distance for patients repeatedly scanned in clinically-relevant arm positions.

  15. MicroPET/CT Imaging of an Orthotopic Model of Human Glioblastoma Multiforme and Evaluation of Pulsed Low-Dose Irradiation

    SciTech Connect

    Park, Sean S.; Chunta, John L.; Robertson, John M.; Martinez, Alvaro A.; Oliver Wong, Ching-Yee; Amin, Mitual; Wilson, George D.; Marples, Brian

    2011-07-01

    Purpose: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Methods: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Results: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 x 10{sup 6} cells produced a 50- to 70-mm{sup 3} tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). Conclusion: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.

  16. Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

    SciTech Connect

    Maier, Joscha; Sawall, Stefan; Kachelrieß, Marc

    2014-05-15

    Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the

  17. SU-E-I-41: Dictionary Learning Based Quantitative Reconstruction for Low-Dose Dual-Energy CT (DECT)

    SciTech Connect

    Xu, Q; Xing, L; Xiong, G; Elmore, K; Min, J

    2015-06-15

    Purpose: DECT collects two sets of projection data under higher and lower energies. With appropriates composition methods on linear attenuation coefficients, quantitative information about the object, such as density, can be obtained. In reality, one of the important problems in DECT is the radiation dose due to doubled scans. This work is aimed at establishing a dictionary learning based reconstruction framework for DECT for improved image quality while reducing the imaging dose. Methods: In our method, two dictionaries were learned respectively from the high-energy and lowenergy image datasets of similar objects under normal dose in advance. The linear attenuation coefficient was decomposed into two basis components with material based composition method. An iterative reconstruction framework was employed. Two basis components were alternately updated with DECT datasets and dictionary learning based sparse constraints. After one updating step under the dataset fidelity constraints, both high-energy and low-energy images can be obtained from the two basis components. Sparse constraints based on the learned dictionaries were applied to the high- and low-energy images to update the two basis components. The iterative calculation continues until a pre-set number of iteration was reached. Results: We evaluated the proposed dictionary learning method with dual energy images collected using a DECT scanner. We re-projected the projection data with added Poisson noise to reflect the low-dose situation. The results obtained by the proposed method were compared with that obtained using FBP based method and TV based method. It was found that the proposed approach yield better results than other methods with higher resolution and less noise. Conclusion: The use of dictionary learned from DECT images under normal dose is valuable and leads to improved results with much lower imaging dose.

  18. Head-to-head coiled arrangement of the subunits of the animal fatty acid synthase.

    PubMed

    Witkowski, Andrzej; Ghosal, Alokesh; Joshi, Anil K; Witkowska, H Ewa; Asturias, Francisco J; Smith, Stuart

    2004-12-01

    The role of the beta-ketoacyl synthase domains in dimerization of the 2505 residue subunits of the multifunctional animal FAS has been evaluated by a combination of crosslinking and characterization of several truncated forms of the protein. Polypeptides containing only the N-terminal 971 residues can form dimers, but polypeptides lacking only the N-terminal 422 residue beta-ketoacyl synthase domain cannot. FAS subunits can be crosslinked with spacer lengths as short as 6 A, via cysteine residues engineered near the N terminus of the full-length polypeptides. The proximity of the N-terminal beta-ketoacyl synthase domains and their essential role in dimerization is consistent with a revised model for the FAS in which a head-to-head arrangement of two coiled subunits facilitates functional interactions between the dimeric beta-ketoacyl synthase and the acyl carrier protein domains of either subunit.

  19. Sparse-view image reconstruction in inverse-geometry CT (IGCT) for fast, low-dose, volumetric dental X-ray imaging

    NASA Astrophysics Data System (ADS)

    Hong, D. K.; Cho, H. S.; Oh, J. E.; Je, U. K.; Lee, M. S.; Kim, H. J.; Lee, S. H.; Park, Y. O.; Choi, S. I.; Koo, Y. S.; Cho, H. M.

    2012-12-01

    As a new direction for computed tomography (CT) imaging, inverse-geometry CT (IGCT) has been recently introduced and is intended to overcome limitations in conventional cone-beam CT (CBCT) such as the cone-beam artifacts, imaging dose, temporal resolution, scatter, cost, and so on. While the CBCT geometry consists of X-rays emanating from a small focal spot and collimated toward a larger detector, the IGCT geometry employs a large-area scanned source array with the Xray beams collimated toward a smaller-area detector. In this research, we explored an effective IGCT reconstruction algorithm based on the total-variation (TV) minimization method and studied the feasibility of the IGCT geometry for potential applications to fast, low-dose volumetric dental X-ray imaging. We implemented the algorithm, performed systematic simulation works, and evaluated the imaging characteristics quantitatively. Although much engineering and validation works are required to achieve clinical implementation, our preliminary results have demonstrated a potential for improved volumetric imaging with reduced dose.

  20. Patient-bounded extrapolation using low-dose priors for volume-of-interest imaging in C-arm CT

    SciTech Connect

    Xia, Y.; Maier, A.; Berger, M.; Hornegger, J.; Bauer, S.

    2015-04-15

    Purpose: Three-dimensional (3D) volume-of-interest (VOI) imaging with C-arm systems provides anatomical information in a predefined 3D target region at a considerably low x-ray dose. However, VOI imaging involves laterally truncated projections from which conventional reconstruction algorithms generally yield images with severe truncation artifacts. Heuristic based extrapolation methods, e.g., water cylinder extrapolation, typically rely on techniques that complete the truncated data by means of a continuity assumption and thus appear to be ad-hoc. It is our goal to improve the image quality of VOI imaging by exploiting existing patient-specific prior information in the workflow. Methods: A necessary initial step prior to a 3D acquisition is to isocenter the patient with respect to the target to be scanned. To this end, low-dose fluoroscopic x-ray acquisitions are usually applied from anterior–posterior (AP) and medio-lateral (ML) views. Based on this, the patient is isocentered by repositioning the table. In this work, we present a patient-bounded extrapolation method that makes use of these noncollimated fluoroscopic images to improve image quality in 3D VOI reconstruction. The algorithm first extracts the 2D patient contours from the noncollimated AP and ML fluoroscopic images. These 2D contours are then combined to estimate a volumetric model of the patient. Forward-projecting the shape of the model at the eventually acquired C-arm rotation views gives the patient boundary information in the projection domain. In this manner, we are in the position to substantially improve image quality by enforcing the extrapolated line profiles to end at the known patient boundaries, derived from the 3D shape model estimate. Results: The proposed method was evaluated on eight clinical datasets with different degrees of truncation. The proposed algorithm achieved a relative root mean square error (rRMSE) of about 1.0% with respect to the reference reconstruction on

  1. Fully automated classification of bone marrow infiltration in low-dose CT of patients with multiple myeloma based on probabilistic density model and supervised learning.

    PubMed

    Martínez-Martínez, Francisco; Kybic, Jan; Lambert, Lukáš; Mecková, Zuzana

    2016-04-01

    This paper presents a fully automated method for the identification of bone marrow infiltration in femurs in low-dose CT of patients with multiple myeloma. We automatically find the femurs and the bone marrow within them. In the next step, we create a probabilistic, spatially dependent density model of normal tissue. At test time, we detect unexpectedly high density voxels which may be related to bone marrow infiltration, as outliers to this model. Based on a set of global, aggregated features representing all detections from one femur, we classify the subjects as being either healthy or not. This method was validated on a dataset of 127 subjects with ground truth created from a consensus of two expert radiologists, obtaining an AUC of 0.996 for the task of distinguishing healthy controls and patients with bone marrow infiltration. To the best of our knowledge, no other automatic image-based method for this task has been published before. PMID:26894595

  2. Very low-dose adult whole-body tumor imaging with F-18 FDG PET/CT

    NASA Astrophysics Data System (ADS)

    Krol, Andrzej; Naveed, Muhammad; McGrath, Mary; Lisi, Michele; Lavalley, Cathy; Feiglin, David

    2015-03-01

    The aim of this study was to evaluate if effective radiation dose due to PET component in adult whole-body tumor imaging with time-of-flight F-18 FDG PET/CT could be significantly reduced. We retrospectively analyzed data for 10 patients with the body mass index ranging from 25 to 50. We simulated F-18 FDG dose reduction to 25% of the ACR recommended dose via reconstruction of simulated shorter acquisition time per bed position scans from the acquired list data. F-18 FDG whole-body scans were reconstructed using time-of-flight OSEM algorithm and advanced system modeling. Two groups of images were obtained: group A with a standard dose of F-18 FDG and standard reconstruction parameters and group B with simulated 25% dose and modified reconstruction parameters, respectively. Three nuclear medicine physicians blinded to the simulated activity independently reviewed the images and compared diagnostic quality of images. Based on the input from the physicians, we selected optimal modified reconstruction parameters for group B. In so obtained images, all the lesions observed in the group A were visible in the group B. The tumor SUV values were different in the group A, as compared to group B, respectively. However, no significant differences were reported in the final interpretation of the images from A and B groups. In conclusion, for a small number of patients, we have demonstrated that F-18 FDG dose reduction to 25% of the ACR recommended dose, accompanied by appropriate modification of the reconstruction parameters provided adequate diagnostic quality of PET images acquired on time-of-flight PET/CT.

  3. Characteristic performance evaluation of a photon counting Si strip detector for low dose spectral breast CT imaging

    PubMed Central

    Cho, Hyo-Min; Barber, William C.; Ding, Huanjun; Iwanczyk, Jan S.; Molloi, Sabee

    2014-01-01

    Purpose: The possible clinical applications which can be performed using a newly developed detector depend on the detector's characteristic performance in a number of metrics including the dynamic range, resolution, uniformity, and stability. The authors have evaluated a prototype energy resolved fast photon counting x-ray detector based on a silicon (Si) strip sensor used in an edge-on geometry with an application specific integrated circuit to record the number of x-rays and their energies at high flux and fast frame rates. The investigated detector was integrated with a dedicated breast spectral computed tomography (CT) system to make use of the detector's high spatial and energy resolution and low noise performance under conditions suitable for clinical breast imaging. The aim of this article is to investigate the intrinsic characteristics of the detector, in terms of maximum output count rate, spatial and energy resolution, and noise performance of the imaging system. Methods: The maximum output count rate was obtained with a 50 W x-ray tube with a maximum continuous output of 50 kVp at 1.0 mA. A109Cd source, with a characteristic x-ray peak at 22 keV from Ag, was used to measure the energy resolution of the detector. The axial plane modulation transfer function (MTF) was measured using a 67 μm diameter tungsten wire. The two-dimensional (2D) noise power spectrum (NPS) was measured using flat field images and noise equivalent quanta (NEQ) were calculated using the MTF and NPS results. The image quality parameters were studied as a function of various radiation doses and reconstruction filters. The one-dimensional (1D) NPS was used to investigate the effect of electronic noise elimination by varying the minimum energy threshold. Results: A maximum output count rate of 100 million counts per second per square millimeter (cps/mm2) has been obtained (1 million cps per 100 × 100 μm pixel). The electrical noise floor was less than 4 keV. The energy resolution

  4. Experimental study on the application of a compressed-sensing (CS) algorithm to dental cone-beam CT (CBCT) for accurate, low-dose image reconstruction

    NASA Astrophysics Data System (ADS)

    Oh, Jieun; Cho, Hyosung; Je, Uikyu; Lee, Minsik; Kim, Hyojeong; Hong, Daeki; Park, Yeonok; Lee, Seonhwa; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

    2013-03-01

    In practical applications of three-dimensional (3D) tomographic imaging, there are often challenges for image reconstruction from insufficient data. In computed tomography (CT); for example, image reconstruction from few views would enable fast scanning with reduced doses to the patient. In this study, we investigated and implemented an efficient reconstruction method based on a compressed-sensing (CS) algorithm, which exploits the sparseness of the gradient image with substantially high accuracy, for accurate, low-dose dental cone-beam CT (CBCT) reconstruction. We applied the algorithm to a commercially-available dental CBCT system (Expert7™, Vatech Co., Korea) and performed experimental works to demonstrate the algorithm for image reconstruction in insufficient sampling problems. We successfully reconstructed CBCT images from several undersampled data and evaluated the reconstruction quality in terms of the universal-quality index (UQI). Experimental demonstrations of the CS-based reconstruction algorithm appear to show that it can be applied to current dental CBCT systems for reducing imaging doses and improving the image quality.

  5. Low kV settings CT angiography (CTA) with low dose contrast medium volume protocol in the assessment of thoracic and abdominal aorta disease: a feasibility study

    PubMed Central

    Talei Franzesi, C; Fior, D; Bonaffini, P A; Minutolo, O; Sironi, S

    2015-01-01

    Objective: To assess the diagnostic quality of low dose (100 kV) CT angiography (CTA), by using ultra-low contrast medium volume (30 ml), for thoracic and abdominal aorta evaluation. Methods: 67 patients with thoracic or abdominal vascular disease underwent multidetector CT study using a 256 slice scanner, with low dose radiation protocol (automated tube current modulation, 100 kV) and low contrast medium volume (30 ml; 4 ml s−1). Density measurements were performed on ascending, arch, descending thoracic aorta, anonymous branch, abdominal aorta, and renal and common iliac arteries. Radiation dose exposure [dose–length product (DLP)] was calculated. A control group of 35 patients with thoracic or abdominal vascular disease were evaluated with standard CTA protocol (automated tube current modulation, 120 kV; contrast medium, 80 ml). Results: In all patients, we correctly visualized and evaluated main branches of the thoracic and abdominal aorta. No difference in density measurements was achieved between low tube voltage protocol (mean attenuation value of thoracic aorta, 304 HU; abdominal, 343 HU; renal arteries, 331 HU) and control group (mean attenuation value of thoracic aorta, 320 HU; abdominal, 339; renal arteries, 303 HU). Radiation dose exposure in low tube voltage protocol was significantly different between thoracic and abdominal low tube voltage studies (490 and 324 DLP, respectively) and the control group (thoracic DLP, 1032; abdomen, DLP 1078). Conclusion: Low-tube-voltage protocol may provide a diagnostic performance comparable with that of the standard protocol, decreasing radiation dose exposure and contrast material volume amount. Advances in knowledge: Low-tube-voltage-setting protocol combined with ultra-low contrast agent volume (30 ml), by using new multidetector-row CT scanners, represents a feasible diagnostic tool to significantly reduce the radiation dose delivered to patients and to preserve renal function

  6. Head-to-head running race simulation alters pacing strategy, performance, and mood state.

    PubMed

    Tomazini, Fabiano; Pasqua, Leonardo A; Damasceno, Mayara V; Silva-Cavalcante, Marcos D; de Oliveira, Fernando R; Lima-Silva, Adriano E; Bertuzzi, Rômulo

    2015-10-01

    The objective of this study was to analyze the influence of the presence and absence of competitors on pacing, overall running performance, and mood state during a self-paced 3-km run. Nine recreational runners participated in this study. They performed the following tests: a) an incremental test to exhaustion to measure the respiratory compensation point (RCP), maximal oxygen uptake, and peak treadmill speed; b) a submaximal speed constant test to measure running economy; and c) two 3-km running time trials performed collectively (COL, head-to-head competition) or individually (IND, performed alone) to establish pacing and running performance. The COL condition was formed of a group of four runners or five runners. Runners were grouped by matched performance times and to retain head-to-head characteristics.A mood state profile questionnaire was completed before and after the 3-km running time trial. The overall performance was better in the COL than in the IND (11.75 ± 0.05 min vs. 12.25 ± 0.06 min, respectively; p = 0.04). The running speeds during the first 500 m were significantly greater in COL (16.8 ± 2.16 km·h−1) than in IND (15.3 ± 2.45 km·h−1) (p = 0.03).The gain in running speed from IND to COL during the first 400 m (i.e. running speed in COL less running speed in IND) was significantly correlated with the RCP (r = 0.88; p = 0.05). The vigor score significantly decreased from pre- to post-running in COL (p=0.05), but not in IND (p=0.20). Additionally, the post running vigor was significantly higher in IND compared to COL (p = 0.03).These findings suggested that the presence of competitors induces a fast start, which results in an improved overall performance and reduced post-exercise vigor scores, compared to an individual run.

  7. Head-to-head running race simulation alters pacing strategy, performance, and mood state.

    PubMed

    Tomazini, Fabiano; Pasqua, Leonardo A; Damasceno, Mayara V; Silva-Cavalcante, Marcos D; de Oliveira, Fernando R; Lima-Silva, Adriano E; Bertuzzi, Rômulo

    2015-10-01

    The objective of this study was to analyze the influence of the presence and absence of competitors on pacing, overall running performance, and mood state during a self-paced 3-km run. Nine recreational runners participated in this study. They performed the following tests: a) an incremental test to exhaustion to measure the respiratory compensation point (RCP), maximal oxygen uptake, and peak treadmill speed; b) a submaximal speed constant test to measure running economy; and c) two 3-km running time trials performed collectively (COL, head-to-head competition) or individually (IND, performed alone) to establish pacing and running performance. The COL condition was formed of a group of four runners or five runners. Runners were grouped by matched performance times and to retain head-to-head characteristics.A mood state profile questionnaire was completed before and after the 3-km running time trial. The overall performance was better in the COL than in the IND (11.75 ± 0.05 min vs. 12.25 ± 0.06 min, respectively; p = 0.04). The running speeds during the first 500 m were significantly greater in COL (16.8 ± 2.16 km·h−1) than in IND (15.3 ± 2.45 km·h−1) (p = 0.03).The gain in running speed from IND to COL during the first 400 m (i.e. running speed in COL less running speed in IND) was significantly correlated with the RCP (r = 0.88; p = 0.05). The vigor score significantly decreased from pre- to post-running in COL (p=0.05), but not in IND (p=0.20). Additionally, the post running vigor was significantly higher in IND compared to COL (p = 0.03).These findings suggested that the presence of competitors induces a fast start, which results in an improved overall performance and reduced post-exercise vigor scores, compared to an individual run. PMID:26013576

  8. Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

    PubMed Central

    Hamm, B; Huppertz, A; Lembcke, A

    2015-01-01

    Objective: To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan. Methods: 30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans. Results: Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively. Conclusion: An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients. Advances in knowledge: Further dose reductions are possible owing to a change in the individual patient's imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure. PMID:25710210

  9. Comparison of 128-Slice Low-Dose Prospective ECG-Gated CT Scanning and Trans-Thoracic Echocardiography for the Diagnosis of Complex Congenital Heart Disease

    PubMed Central

    Bu, Guilin; Miao, Ying; Bin, Jingwen; Deng, Sheng; Liu, Taowen; Jiang, Hongchun; Chen, Weiping

    2016-01-01

    Objective To compare prospective ECG-gated multi-slice computed tomography (MSCT) and trans-thoracic echocardiography (TTE) in the diagnosis of complex congenital heart disease (CHD). Methods This was a prospective study of consecutive patients with complex CHD (age <7 years) treated at a tertiary hospital between May 2013 and May 2015. All patients were imaged with TTE and prospective ECG-gated 128-slice spiral CT in the week before surgery. Effective radiation dose (ED) was calculated from volume CT dose index (CTDIvol) and dose length product (DLP). Image quality (5-point scale) was assessed independently by two radiologists. Using surgical findings as the reference, the diagnostic capabilities of MSCT and TTE were compared. Results Thirty-five patients (19 males) aged 1.59±1.58 years (range, 3 days to 74 months) were included. CTDIvol, DLP and ED were 0.90±0.24 mGy, 12.9±4.7 mGy∙cm and 0.64±0.21 mSv (range, 0.358–1.196 mSv), respectively. Image quality score was 4.3±0.5, and all images met the diagnostic requirements. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing CHD were 97.2%, 99.8%, 99.0%, and 99.5%, respectively, for MSCT, and 90.6%, 99.8%, 99.0%, and 98.4%, respectively, for TTE. MSCT not only had a higher sensitivity than TTE overall (97.2% vs. 90.6%; P<0.05), but was much more sensitive for the diagnosis of extracardiac vascular abnormalities (92.0% vs. 68.0%; P<0.05). Conclusion 128-slice low-dose prospective ECG-gated CT scanning has important clinical value in the diagnosis of complex CHD in children, complementing and extending the findings of TTE. PMID:27788237

  10. Low-Dose (10%) Computed Tomography May Be Inferior to Standard-Dose CT in the Evaluation of Acute Renal Colic in the Emergency Room Setting

    PubMed Central

    Han, Esther; Atalla, Christopher S.; Santucci, Richard A.; O'Neil, Brian; Wynberg, Jason B.

    2016-01-01

    Abstract Introduction: Noncontrast CT is the standard of care to evaluate nephrolithiasis. We evaluated the performance of low-dose CT (LDCT) scan for evaluation of renal colic in the emergency room (ER). Materials and Methods: Patients visiting the ER with suspected nephrolithiasis received a standard-dose CT (SDCT) and an LDCT. Two urologists read the LDCTs and later they read SDCTs. Stone information was recorded on a diagram of the renal system. Findings on SDCTs and LDCTs were correlated through side-by-side comparison of the diagrams. Later, the two urologists adjudicated all nonconcordance between SDCTs and LDCTs in an unblinded manner. Results: Twenty-seven patients were included. SDCTs revealed 27 stones in 18 patients. Mean stone size was 3.81 mm. LDCTs revealed 27 stones in 18 patients with a mean stone size of 4.7 mm (p = 0.23). Overall sensitivity and specificity of LDCTs were 70% and 39%, respectively. There were eight false-positive and eight false-negative stones. All the false-positive stones on LDCTs were placed in the ureter, in which all of the corresponding SDCTs were visible calcifications outside the ureter. Of the eight false-negative stones on LDCTs, seven were visible calcifications on the SDCTs and the eighth stone was 1 mm and was not visible. Conclusion: LDCT may not perform well in the evaluation of suspected nephrolithiasis in the acute setting. LDCT scan accurately demonstrates calcifications; however, accurate placement of calcifications in or out of the urinary tract may be diminished due to impaired resolution of soft tissue structures. PMID:26728321

  11. Head-to-Head Comparison of Anti-Inflammatory Performance of Known Natural Products In Vitro

    PubMed Central

    Allijn, Iris E.; Vaessen, Stefan F. C.; Quarles van Ufford, Linda C.; Beukelman, Kees J.; de Winther, Menno P. J.; Storm, Gert; Schiffelers, Raymond M.

    2016-01-01

    Inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of inflammatory disorders. However, steroidal drugs can also exert a broad range of side effects and appear not always effective. This calls for the development of alternative drugs with a different mechanism of action, which are likely to be found in the field of natural products (NPs). For many NPs strong anti-inflammatory effects have been described, but usually investigating a single compound in a single assay. In this study, eight promising NPs were selected and tested against the strong anti-inflammatory drug prednisolone. For this head-to-head comparison, in vitro assays were used which represent different pathways of the inflammatory response: TNF-α and IL-6 expression by macrophages, IL-8 expression by colon epithelial cells, ROS production in polymorphonuclear leukocytes and platelet activation in whole blood. Performance profiles were established which allowed us to identify curcumin, berberine chloride and epigallocatechin gallate as potential alternatives for prednisolone or other glucocorticoids in inflammation. PMID:27163931

  12. A Head-to-head Comparison between SurgiMend and Epiflex in 127 Breast Reconstructions

    PubMed Central

    Vogt, Nadine; Brunnert, Klaus; Sauerwald, Axel; Puppe, Julian; Warm, Mathias

    2015-01-01

    Background: The use of acellular dermal matrices (ADM) has become a widely used option in breast reconstruction. A great deal of literature is available, totaling over 2400 ADM reconstructions. Nonetheless, head-to-head comparisons between SurgiMend and Epiflex are not yet reported. In fact, this is the first clinical data report on the use of Epiflex. This work will, therefore, compare postoperative complication rates and costs for these ADMs. Methods: This analysis is a retrospective review of a single surgeon’s 6-year experience with both SurgiMend—an acellular bovine dermal collagen matrix for soft-tissue reconstruction and Epiflex—a decellularized human skin tissue from 2008 to 2013. Results: One hundred patients had a total of 127 implant-based reconstructions using SurgiMend (64 cases; 50.4%) or Epiflex (63 cases; 49.6%). Gross complication rates were 11.1% for SurgiMend and 40.6% for Epiflex including hematoma, postoperative skin irritation, infection, necrosis, and revision surgery. The most common complication was postoperative red breast syndrome. Severe complications requiring revision surgery were significantly increased in patients treated with Epiflex (12.5%) compared with SurgiMend (4.8%). Conclusions: This retrospective analysis favors the use of SurgiMend over Epiflex because of significantly lower gross complication rates. Severe complication rates are comparable with those reported in literature for both products. Although results promote the use of SurgiMend, the single surgeon retrospective nature of this work limits its clinical impact. PMID:26180740

  13. POP-pincer osmium-polyhydrides: head-to-head (Z)-dimerization of terminal alkynes.

    PubMed

    Alós, Joaquín; Bolaño, Tamara; Esteruelas, Miguel A; Oliván, Montserrat; Oñate, Enrique; Valencia, Marta

    2013-05-20

    A wide range of osmium-polyhydride complexes stabilized by the POP-pincer ligand xant(P(i)Pr2)2 (9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene) have been synthesized through cis-OsCl2{κ-S-(DMSO)4} (1, DMSO = dimethyl sulfoxide). Treatment of toluene solutions of this adduct with the diphosphine, under reflux, leads to OsCl2{xant(P(i)Pr2)2}(κ-S-DMSO) (2). The reaction of 2 with H2 in the presence of Et3N affords OsH3Cl{xant(P(i)Pr2)2} (3), which can be also prepared by addition of xant(P(i)Pr2)2 to toluene solutions of the unsaturated d(4)-trihydride OsH3Cl(P(i)Pr3)2 (5). Complex 3 reductively eliminates H2 in toluene at 90 °C. In the presence of dimethyl sulfoxide, the resulting monohydride is trapped by the S-donor molecule to give OsHCl{xant(P(i)Pr2)2}(κ-S-DMSO) (6). The reaction of 2 with H2 is sensible to the Brønsted base. Thus, in contrast to Et3N, NaH removes both chloride ligands and the hexahydride OsH6{xant(P(i)Pr2)2} (7), containing a κ(2)-P-binding diphosphine, is formed under 3 atm of hydrogen at 50 °C. Complex 7 releases a H2 molecule to yield the tetrahydride OsH4{xant(P(i)Pr2)2} (8), which can be also prepared by reaction of OsH6(P(i)Pr3)2 (9) with xant(P(i)Pr2)2. Complex 8 reduces H(+) to give, in addition to H2, the oxidized OsH4-species [OsH4(OTf){xant(P(i)Pr2)2}](+) (10, OTf = trifluoromethanesulfonate). The redox process occurs in two stages via the OsH5-cation [OsH5{xant(P(i)Pr2)2}](+) (11). The metal oxidation state four can be recovered. The addition of acetonitrile to 10 leads to [OsH2(η(2)-H2)(CH3CN){xant(P(i)Pr2)2}](2+) (12). The deprotonation of 12 yields the osmium(IV) trihydride [OsH3(CH3CN){xant(P(i)Pr2)2}](+) (13), which is also formed by addition of HOTf to the acetonitrile solutions of 8. The latter is further an efficient catalyst precursor for the head-to-head (Z)-dimerization of phenylacetylene and tert-butylacetylene. During the activation process of the tetrahydride, the bis(alkynyl)vinylidene derivatives Os

  14. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial

    PubMed Central

    Patz, Edward F; Greco, Erin; Gatsonis, Constantine; Pinsky, Paul; Kramer, Barnett S; Aberle, Denise R

    2016-01-01

    Summary Background Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. Methods We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55–74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385. Findings Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97–408·26] per 100 000 person-years vs 661·23 [622·07–702·21]) and had lower lung cancer

  15. WE-G-18A-04: 3D Dictionary Learning Based Statistical Iterative Reconstruction for Low-Dose Cone Beam CT Imaging

    SciTech Connect

    Bai, T; Yan, H; Shi, F; Jia, X; Jiang, Steve B.; Lou, Y; Xu, Q; Mou, X

    2014-06-15

    Purpose: To develop a 3D dictionary learning based statistical reconstruction algorithm on graphic processing units (GPU), to improve the quality of low-dose cone beam CT (CBCT) imaging with high efficiency. Methods: A 3D dictionary containing 256 small volumes (atoms) of 3x3x3 voxels was trained from a high quality volume image. During reconstruction, we utilized a Cholesky decomposition based orthogonal matching pursuit algorithm to find a sparse representation on this dictionary basis of each patch in the reconstructed image, in order to regularize the image quality. To accelerate the time-consuming sparse coding in the 3D case, we implemented our algorithm in a parallel fashion by taking advantage of the tremendous computational power of GPU. Evaluations are performed based on a head-neck patient case. FDK reconstruction with full dataset of 364 projections is used as the reference. We compared the proposed 3D dictionary learning based method with a tight frame (TF) based one using a subset data of 121 projections. The image qualities under different resolutions in z-direction, with or without statistical weighting are also studied. Results: Compared to the TF-based CBCT reconstruction, our experiments indicated that 3D dictionary learning based CBCT reconstruction is able to recover finer structures, to remove more streaking artifacts, and is less susceptible to blocky artifacts. It is also observed that statistical reconstruction approach is sensitive to inconsistency between the forward and backward projection operations in parallel computing. Using high a spatial resolution along z direction helps improving the algorithm robustness. Conclusion: 3D dictionary learning based CBCT reconstruction algorithm is able to sense the structural information while suppressing noise, and hence to achieve high quality reconstruction. The GPU realization of the whole algorithm offers a significant efficiency enhancement, making this algorithm more feasible for potential

  16. Computer-aided diagnostic scheme for distinction between benign and malignant nodules in thoracic low-dose CT by use of massive training artificial neural network.

    PubMed

    Suzuki, Kenji; Li, Feng; Sone, Shusuke; Doi, Kunio

    2005-09-01

    Low-dose helical computed tomography (LDCT) is being applied as a modality for lung cancer screening. It may be difficult, however, for radiologists to distinguish malignant from benign nodules in LDCT. Our purpose in this study was to develop a computer-aided diagnostic (CAD) scheme for distinction between benign and malignant nodules in LDCT scans by use of a massive training artificial neural network (MTANN). The MTANN is a trainable, highly nonlinear filter based on an artificial neural network. To distinguish malignant nodules from six different types of benign nodules, we developed multiple MTANNs (multi-MTANN) consisting of six expert MTANNs that are arranged in parallel. Each of the MTANNs was trained by use of input CT images and teaching images containing the estimate of the distribution for the "likelihood of being a malignant nodule," i.e., the teaching image for a malignant nodule contains a two-dimensional Gaussian distribution and that for a benign nodule contains zero. Each MTANN was trained independently with ten typical malignant nodules and ten benign nodules from each of the six types. The outputs of the six MTANNs were combined by use of an integration ANN such that the six types of benign nodules could be distinguished from malignant nodules. After training of the integration ANN, our scheme provided a value related to the "likelihood of malignancy" of a nodule, i.e., a higher value indicates a malignant nodule, and a lower value indicates a benign nodule. Our database consisted of 76 primary lung cancers in 73 patients and 413 benign nodules in 342 patients, which were obtained from a lung cancer screening program on 7847 screenees with LDCT for three years in Nagano, Japan. The performance of our scheme for distinction between benign and malignant nodules was evaluated by use of receiver operating characteristic (ROC) analysis. Our scheme achieved an Az (area under the ROC curve) value of 0.882 in a round-robin test. Our scheme correctly

  17. Nanomedicines for Inflammatory Arthritis: Head-To-Head Comparison of Glucocorticoid-Containing Polymers, Micelles and Liposomes

    PubMed Central

    Crielaard, Bart J.; Dusad, Anand; Lele, Subodh M.; Rijcken, Cristianne J. F.; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R.; Hennink, Wim E.; Storm, Gert; Lammers, Twan; Wang, Dong

    2014-01-01

    As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research. PMID:24341611

  18. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  19. SU-C-207-03: Optimization of a Collimator-Based Sparse Sampling Technique for Low-Dose Cone-Beam CT

    SciTech Connect

    Lee, T; Cho, S; Kim, I; Han, B

    2015-06-15

    Purpose: In computed tomography (CT) imaging, radiation dose delivered to the patient is one of the major concerns. Sparse-view CT takes projections at sparser view angles and provides a viable option to reducing dose. However, a fast power switching of an X-ray tube, which is needed for the sparse-view sampling, can be challenging in many CT systems. We have earlier proposed a many-view under-sampling (MVUS) technique as an alternative to sparse-view CT. In this study, we investigated the effects of collimator parameters on the image quality and aimed to optimize the collimator design. Methods: We used a bench-top circular cone-beam CT system together with a CatPhan600 phantom, and took 1440 projections from a single rotation. The multi-slit collimator made of tungsten was mounted on the X-ray source for beam blocking. For image reconstruction, we used a total-variation minimization (TV) algorithm and modified the backprojection step so that only the measured data through the collimator slits are to be used in the computation. The number of slits and the reciprocation frequency have been varied and the effects of them on the image quality were investigated. We also analyzed the sampling efficiency: the sampling density and data incoherence in each case. We tested three sets of slits with their number of 6, 12 and 18, each at reciprocation frequencies of 10, 30, 50 and 70 Hz/ro. Results: Consistent results in the image quality have been produced with the sampling efficiency, and the optimum condition was found to be using 12 slits at 30 Hz/ro. As image quality indices, we used the CNR and the detectability. Conclusion: We conducted an experiment with a moving multi-slit collimator to realize a sparse-sampled cone-beam CT. Effects of collimator parameters on the image quality have been systematically investigated, and the optimum condition has been reached.

  20. Brain metastases detectability of routine whole body (18)F-FDG PET and low dose CT scanning in 2502 asymptomatic patients with solid extracranial tumors.

    PubMed

    Bochev, Pavel; Klisarova, Aneliya; Kaprelyan, Ara; Chaushev, Borislav; Dancheva, Zhivka

    2012-01-01

    As fluorine-18-fluorodesoxyglucose positron emission tomography/computed tomography ( (18)F-FDG PET/CT) is gaining wider availability, more and more patients with malignancies undergo whole body PET/CT, mostly to assess tumor spread in the rest of the body, but not in the brain. Brain is a common site of metastatic spread in patients with solid extracranial tumors. Gold standard in the diagnosis of brain metastases remains magnetic resonance imaging (MRI). However MRI is not routinely indicated and is not available for all cancer patients. Fluorine-18-FDG PET is considered as having poor sensitivity in detecting brain metastases, but this may not be true for PET/CT. The aim of our study was to assess the value of (18)F-FDG PET/CT in the detection of brain metastases found by whole body scan including the brain, in patients with solid extracranial neoplasms. A total of 2502 patients with solid extracranial neoplasms were studied. All patients underwent a routine whole body (18)F-FDG PET/CT scan with the whole brain included in the scanned field. Patients with known or suspected brain metastases were preliminary excluded from the study. Hypermetabolic and ring-like brain lesions on the PET scan were considered as metastases. Lesions with CT characteristics of brain metastases were regarded as such irrespective of their metabolic pattern. Lesions in doubt were verified by MRI during first testing or on follow-up or by operation. Our results showed that brain lesions, indicative of and verified to be metastases were detected in 25 out of the 2502 patients (1%), with lung cancer being the most common primary. Twenty three out of these 25 patients had no neurological symptoms by the time of the scan. The detection rate of brain metastases was relatively low, but information was obtained with a minimum increase of radiation burden. In conclusion, whole body (18)F-FDG PET/CT detected brain metastases in 1% of the patients if brain was included in the scanned field. Brain

  1. Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT.

    PubMed

    Gnagnarella, Patrizia; Maisonneuve, Patrick; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia

    2013-06-01

    The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

  2. Compressed-sensing (CS)-based 3D image reconstruction in cone-beam CT (CBCT) for low-dose, high-quality dental X-ray imaging

    NASA Astrophysics Data System (ADS)

    Lee, M. S.; Kim, H. J.; Cho, H. S.; Hong, D. K.; Je, U. K.; Oh, J. E.; Park, Y. O.; Lee, S. H.; Cho, H. M.; Choi, S. I.; Koo, Y. S.

    2013-09-01

    The most popular reconstruction algorithm for cone-beam computed tomography (CBCT) is based on the computationally-inexpensive filtered-backprojection (FBP) method. However, that method usually requires dense projections over the Nyquist samplings, which imposes severe restrictions on the imaging doses. Moreover, the algorithm tends to produce cone-beam artifacts as the cone angle is increased. Several variants of the FBP-based algorithm have been developed to overcome these difficulties, but problems with the cone-beam reconstruction still remain. In this study, we considered a compressed-sensing (CS)-based reconstruction algorithm for low-dose, high-quality dental CBCT images that exploited the sparsity of images with substantially high accuracy. We implemented the algorithm and performed systematic simulation works to investigate the imaging characteristics. CBCT images of high quality were successfully reconstructed by using the built-in CS-based algorithm, and the image qualities were evaluated quantitatively in terms of the universal-quality index (UQI) and the slice-profile quality index (SPQI).We expect the reconstruction algorithm developed in the work to be applicable to current dental CBCT systems, to reduce imaging doses, and to improve the image quality further.

  3. Head-To-Head Comparison of Different Solubility-Enabling Formulations of Etoposide and Their Consequent Solubility-Permeability Interplay.

    PubMed

    Beig, Avital; Miller, Jonathan M; Lindley, David; Carr, Robert A; Zocharski, Philip; Agbaria, Riad; Dahan, Arik

    2015-09-01

    The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility-permeability interplay. The low-solubility anticancer drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility-permeability interplay. All formulations significantly increased etoposide's apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility-permeability tradeoff associated with other formulation techniques. Accounting for the solubility-permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs.

  4. SU-E-I-39: Combining Conventional Tomographic Imaging Strategy and Interior Tomography for Low Dose Dual-Energy CT (DECT)

    SciTech Connect

    Xu, Q; Xing, L; Xiong, G; Elmore, K; Min, J

    2015-06-15

    Purpose: Dual-energy CT (DECT) affords quantitative information of tissue density and provides a new dimension for disease diagnosis and treatment planning. The technique, however, increases the imaging dose because of the doubled scans, and thus hinders its widespread clinical applications. The purpose of this work is to develop a novel hybrid DECT image acquisition and reconstruction strategy, in which one of the energies is dealt by interior tomography while the other one is obtained using conventional tomography approach. Methods: In the proposed hybrid imaging strategy, the projection data of one of the energies (e.g., high-energy) were acquired and processed in an interior scanning model, whereas the other energy in the conventional tomographic approach. It known that, if the ROI is piecewise constant or polynomial, the interior ROI can be reconstructed with TV or HOT minimization. Here we extend the TV based interior reconstruction method into dual-energy situation. The ROI images so obtained were overlaid in the context of conventional CT of the companion energy. A material based composition in ROI was used in the proposed reconstruction framework. Results: In the simulation experiment with a diagnostic DECT geometry and energies, we were able to derive the densities of soft-tissues and bones in the ROI with high fidelity. In the experimental CBCT study, both kV and MV data were collected using the on-board kV and MV imaging system. The MV data were truncated only across the ROI. Using the interior tomography reconstruction above, we were able to obtain the ROI images as that obtained using un-truncated MV data with known tissue densities. Conclusion: The proposed DECT imaging strategy provides an effective way to extract tissue density information in the ROI and in the context of anatomical images of CT imaging, with much reduced imaging dose.

  5. Evaluation of a Chest Circumference-Adapted Protocol for Low-Dose 128-Slice Coronary CT Angiography with Prospective Electrocardiogram Triggering

    PubMed Central

    Lu, Chenying; Wang, Zufei; Wang, Hailin; Hu, Xianghua; Chen, Chunmiao

    2015-01-01

    Objective To assess the effect of chest circumference-adapted scanning protocol on radiation exposure and image quality in patients undergoing prospective electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). Materials and Methods One hundred-eighty-five consecutive patients, who had undergone prospective ECG triggering CCTA with a 128-slice CT, were included in the present study. Nipple-level chest circumference, body weight and height were measured before CT examinations. Patients were divided into four groups based on kV/ref·mAs = 100/200, 100/250, 120/200, and 120/250, when patient's chest circumference was ≤ 85.0 (n = 56), 85.0-90.0 (n = 53), 90.0-95.0 (n = 44), and > 95.0 (n = 32), respectively. Image quality per-segment was independently assessed by two experienced observers. Image noise and attenuation were also measured. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The effective radiation dose was calculated using CT dose volume index and the dose-length product. Results A significant correlation was observed between patients' chest circumference and body mass index (r = 0.762, p < 0.001). Chest circumference ranged from 74 to 105 cm, and the mean effective radiation dose was 1.9-3.8 mSv. Diagnostic image quality was obtained in 98.5% (2440/2478) of all evaluated coronary segments without any significant differences among the four groups (p = 0.650). No significant difference in image noise was observed among the four groups (p = 0.439), thus supporting the validity of the chest circumference-adapted scanning protocol. However, vessel attenuation, SNR and CNR were significantly higher in the 100 kV groups than in the 120 kV groups (p < 0.05). Conclusion A measure of chest circumference can be used to adapt tube voltage and current for individualized radiation dose control, with resultant similar image noise and sustained diagnostic image quality. PMID:25598671

  6. Preliminary performance of image quality for a low-dose C-arm CT system with a flat-panel detector

    NASA Astrophysics Data System (ADS)

    Kyung Cha, Bo; Seo, Chang-Woo; Yang, Keedong; Jeon, Seongchae; Huh, Young

    2015-06-01

    Digital flat panel imager (FPI)-based cone-beam computed tomography (CBCT) has been widely used in C-arm imaging for spine surgery and interventional procedures. The system provides real-time fluoroscopy with high spatial resolution and three-dimensional (3D) visualization of anatomical structure without the need for patient transportation in interventional suite. In this work, a prototype CBCT imaging platform with continuous single rotation about the gantry was developed by using a large-area flat-panel detector with amorphous Si-based thin film transistor matrix. The different 2D projection images were acquired during constant gantry velocity for reconstructed images at a tube voltage of 80-120 kVp, and different current (10-50 mA) conditions. Various scan protocols were applied to a chest phantom human by changing the number of projection images and scanning angles. The projections were then reconstructed into a volumetric data of sections by using a 3D reconstruction algorithm (e.g., filtered back projection). The preliminary quantitative X-ray performance of our CBCT system was investigated by using the American Association of Physicists in Medicine CT phantom in terms of spatial resolution, contrast resolution, and CT number linearity for mobile or fixed C-arm based CBCT application with limited rotational geometry. The novel results of the projection data with different scanning angles and angular increments in the orbital gantry platform were acquired and evaluated experimentally.

  7. SU-F-18C-13: Low-Dose X-Ray CT Reconstruction Using a Hybrid First-Order Method

    SciTech Connect

    Liu, L; Lin, W; Jin, M

    2014-06-15

    Purpose: To develop a novel reconstruction method for X-ray CT that can lead to accurate reconstruction at significantly reduced dose levels combining low X-ray incident intensity and few views of projection data. Methods: The noise nature of the projection data at low X-ray incident intensity was modeled and accounted by the weighted least-squares (WLS) criterion. The total variation (TV) penalty was used to mitigate artifacts caused by few views of data. The first order primal-dual (FOPD) algorithm was used to minimize TV in image domain, which avoided the difficulty of the non-smooth objective function. The TV penalized WLS reconstruction was achieved by alternated FOPD TV minimization and projection onto convex sets (POCS) for data fidelity constraints. The proposed FOPD-POCS method was evaluated using the FORBILD jaw phantom and the real cadaver head CT data. Results: The quantitative measures, root mean square error (RMSE) and contrast-to-noise ratio (CNR), demonstrate the superior denoising capability of WLS over LS-based TV iterative reconstruction. The improvement of RMSE (WLS vs. LS) is 15%∼21% and that of CNR is 17%∼72% when the incident counts per ray are ranged from 1×10{sup 5} to 1×10{sup 3}. In addition, the TV regularization can accurately reconstruct images from about 50 views of the jaw phantom. The FOPD-POCS reconstruction reveals more structural details and suffers fewer artifacts in both the phantom and real head images. The FOPD-POCS method also shows fast convergence at low X-ray incident intensity. Conclusion: The new hybrid FOPD-POCS method, based on TV penalized WLS, yields excellent image quality when the incident X-ray intensity is low and the projection views are limited. The reconstruction is computationally efficient since the FOPD minimization of TV is applied only in the image domain. The characteristics of FOPD-POCS can be exploited to significantly reduce radiation dose of X-ray CT without compromising accuracy for diagnosis

  8. A Fused α-β “Mini-spectrin” Mimics the Intact Erythrocyte Spectrin Head-to-head Tetramer*

    PubMed Central

    Harper, Sandra L.; Li, Donghai; Maksimova, Yelena; Gallagher, Patrick G.; Speicher, David W.

    2010-01-01

    Head-to-head assembly of two spectrin heterodimers to form an actin-cross-linking tetramer is a physiologically dynamic interaction that contributes to red cell membrane integrity. Recombinant β-spectrin C-terminal and α-spectrin N-terminal peptides can form tetramer-like univalent complexes, but they cannot evaluate effects of the open-closed dimer interactions or lateral associations of the two-spectrin strands on tetramer formation. In this study we produced and characterized a fused “mini-spectrin dimer” containing the β-spectrin C-terminal region linked to the α-spectrin N-terminal region. This fused mini-spectrin mimics structural and functional properties of intact, full-length dimers and tetramers, including lateral association of the α and β subunits in the dimer and formation of a closed dimer. High performance liquid chromatography gel filtration analyses of this mini-spectrin provide the first direct non-imaging experimental evidence for open and closed spectrin dimers and show that dimer-tetramer-oligomer interconversion is slow at low temperatures and accelerated at 30 °C, analogous to full-length spectrin. This protein exhibits wild type dimer-tetramer dissociation constants of ∼1 μm at 30 °C, independent of initial oligomeric state. Conformational states of the mini-spectrin dimer were probed further using chemical cross-linking, which identified distinct groups of cross-links for “open” and “closed” dimers and confirmed the N-terminal region of α-spectrin remains highly flexible in the complex, exhibiting closely analogous structures to those observed for the isolated α-spectrin N-terminal using NMR (Park, S., Caffrey, M. S., Johnson, M. E., and Fung, L. W. (2003) J. Biol. Chem. 278, 21837–21844). This fusion protein should serve as a useful template for structural and functional studies of the divalent tetramer site. PMID:20139081

  9. Lung Cancer Screening with Low Dose CT

    PubMed Central

    Caroline, Chiles

    2014-01-01

    SUMMARY The announcement of the results of the NLST, showing a 20% reduction in lung-cancer specific mortality with LDCT screening in a high risk population, marked a turning point in lung cancer screening. This was the first time that a randomized controlled trial had shown a mortality reduction with an imaging modality aimed at early detection of lung cancer. Current guidelines endorse LDCT screening for smokers and former smokers ages 55 to 74, with at least a 30 pack year smoking history. Adherence to published algorithms for nodule follow-up is strongly encouraged. Future directions for screening research include risk stratification for selection of the screening population, and improvements in the diagnostic follow-up for indeterminate pulmonary nodules. As with screening for other malignancies, screening for lung cancer with LDCT has revealed that there are indolent lung cancers which may not be fatal. More research is necessary if we are to maximize the risk-benefit ratio in lung cancer screening. PMID:24267709

  10. Charge compensation of head-to-head and tail-to-tail domain walls in barium titanate and its influence on conductivity

    SciTech Connect

    Zuo, Yinan; Genenko, Yuri A.; Xu, Bai-Xiang

    2014-07-28

    The effect of the polarization charge compensation by ionic and electronic space charges on domain properties in ferroelectrics with semiconducting features is considered, in particular, the conductivity of head-to-head and tail-to-tail domain walls is studied. It is shown that the domain wall conductivity that is enhanced by electrons or holes depends on the configuration and the types of domains as well as on the energy levels and concentrations of the defects involved. Phase field simulation results are used to explain recent equivocal experimental results on conductivity of charged domain walls in different ferroelectrics.

  11. A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

    PubMed Central

    Kresovic, Darko; Schempp, Florence; Cheikh-Ali, Zakaria

    2015-01-01

    Summary The biosynthesis of photopyrones, novel quorum sensing signals in Photorhabdus, has been studied by heterologous expression of the photopyrone synthase PpyS catalyzing the head-to-head condensation of two acyl moieties. The biochemical mechanism of pyrone formation has been investigated by amino acid exchange and bioinformatic analysis. Additionally, the evolutionary origin of PpyS has been studied by phylogenetic analyses also revealing homologous enzymes in Pseudomonas sp. GM30 responsible for the biosynthesis of pseudopyronines including a novel derivative. Moreover this novel class of ketosynthases is only distantly related to other pyrone-forming enzymes identified in the biosynthesis of the potent antibiotics myxopyronin and corallopyronin. PMID:26425196

  12. TU-A-12A-12: Improved Airway Measurement Accuracy for Low Dose Quantitative CT (qCT) Using Statistical (ASIR), at Reduced DFOV, and High Resolution Kernels in a Phantom and Swine Model

    SciTech Connect

    Yadava, G; Imai, Y; Hsieh, J

    2014-06-15

    Purpose: Quantitative accuracy of Iodine Hounsfield Unit (HU) in conventional single-kVp scanning is susceptible to beam-hardening effect. Dual-energy CT has unique capabilities of quantification using monochromatic CT images, but this scanning mode requires the availability of the state-of-the-art CT scanner and, therefore, is limited in routine clinical practice. Purpose of this work was to develop a beam-hardening-correction (BHC) for single-kVp CT that can linearize Iodine projections at any nominal energy, apply this approach to study Iodine response with respect to keV, and compare with dual-energy based monochromatic images obtained from material-decomposition using 80kVp and 140kVp. Methods: Tissue characterization phantoms (Gammex Inc.), containing solid-Iodine inserts of different concentrations, were scanned using GE multi-slice CT scanner at 80, 100, 120, and 140 kVp. A model-based BHC algorithm was developed where Iodine was estimated using re-projection of image volume and corrected through an iterative process. In the correction, the re-projected Iodine was linearized using a polynomial mapping between monochromatic path-lengths at various nominal energies (40 to 140 keV) and physically modeled polychromatic path-lengths. The beam-hardening-corrected 80kVp and 140kVp images (linearized approximately at effective energy of the beam) were used for dual-energy material-decomposition in Water-Iodine basis-pair followed by generation of monochromatic images. Characterization of Iodine HU and noise in the images obtained from singlekVp with BHC at various nominal keV, and corresponding dual-energy monochromatic images, was carried out. Results: Iodine HU vs. keV response from single-kVp with BHC and dual-energy monochromatic images were found to be very similar, indicating that single-kVp data may be used to create material specific monochromatic equivalent using modelbased projection linearization. Conclusion: This approach may enable quantification of

  13. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    SciTech Connect

    Yan, Hao E-mail: xun.jia@utsouthwestern.edu; Shi, Feng; Jiang, Steve B.; Jia, Xun E-mail: xun.jia@utsouthwestern.edu; Wang, Xiaoyu; Cervino, Laura; Bai, Ti; Folkerts, Michael

    2014-11-01

    , an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. Conclusions: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation.

  14. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    PubMed Central

    Yan, Hao; Wang, Xiaoyu; Shi, Feng; Bai, Ti; Folkerts, Michael; Cervino, Laura; Jiang, Steve B.; Jia, Xun

    2014-01-01

    , an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. Conclusions: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation. PMID:25370645

  15. WE-G-18A-01: JUNIOR INVESTIGATOR WINNER - Low-Dose C-Arm Cone-Beam CT with Model-Based Image Reconstruction for High-Quality Guidance of Neurosurgical Intervention

    SciTech Connect

    Wang, A; Stayman, J; Otake, Y; Gallia, G; Siewerdsen, J

    2014-06-15

    improvement in image quality, dose reduction, and reconstruction time of ∼4 min will enable practical deployment of low-dose C-arm CBCT within the operating room. AAPM Research Seed Funding (2013-2014); NIH Fellowship F32EB017571; Siemens Healthcare (XP Division)

  16. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis

    PubMed Central

    Rummel-Kluge, Christine; Komossa, Katja; Schwarz, Sandra; Hunger, Heike; Schmid, Franziska; Lobos, Claudia Asenjo; Kissling, Werner; Davis, John M; Leucht, Stefan

    2010-01-01

    Objective The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine. Method We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis. Results We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine. Conclusions Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient. PMID:20692814

  17. Asbestos Surveillance Program Aachen (ASPA): initial results from baseline screening for lung cancer in asbestos-exposed high-risk individuals using low-dose multidetector-row CT.

    PubMed

    Das, Marco; Mühlenbruch, Georg; Mahnken, Andreas H; Hering, K G; Sirbu, H; Zschiesche, W; Knoll, Lars; Felten, Michael K; Kraus, Thomas; Günther, Rolf W; Wildberger, Joachim E

    2007-05-01

    The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAs(eff.); 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population.

  18. 2,5-Dialkylresorcinol Biosynthesis in Pseudomonas aurantiaca: Novel Head-to-Head Condensation of Two Fatty Acid-Derived Precursors

    PubMed Central

    Nowak-Thompson, Brian; Hammer, Philip E.; Hill, D. Steven; Stafford, Jill; Torkewitz, Nancy; Gaffney, Thomas D.; Lam, Stephen T.; Molnár, István; Ligon, James M.

    2003-01-01

    2-Hexyl-5-propylresorcinol is the predominant analog of several dialkylresorcinols produced by Pseudomonas aurantiaca (Pseudomonas fluorescens BL915). We isolated and characterized three biosynthetic genes that encode an acyl carrier protein, a β-ketoacyl-acyl carrier protein synthase III, and a protein of unknown function, all of which collectively allow heterologous production of 2-hexyl-5-propylresorcinol in Escherichia coli. Two regulatory genes exhibiting similarity to members of the AraC family of transcriptional regulators are also present in the identified gene cluster. Based on the deduced functions of the proteins encoded by the gene cluster and the observed incorporation of labeled carbons from octanoic acid into 2-hexyl-5-propylresorcinol, we propose that dialkylresorcinols are derived from medium-chain-length fatty acids by an unusual head-to-head condensation of β-ketoacyl thioester intermediates. Genomic evidence suggests that there is a similar pathway for the biosynthesis of the flexirubin-type pigments in certain bacteria belonging to the order Cytophagales. PMID:12533461

  19. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

    PubMed

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

  20. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps

    NASA Astrophysics Data System (ADS)

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P.; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-10-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

  1. H3N2 Mismatch of 2014–15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps

    PubMed Central

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P.; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014–15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009–10, 2010–11 and 2014–15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014–15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014–15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model. PMID:26472175

  2. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

    PubMed

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model. PMID:26472175

  3. Two-dimensional electron gases at head-to-head and tail-to-tail domain walls in ferroelectric thin films

    NASA Astrophysics Data System (ADS)

    García-Fernández, Pablo; Íñiguez, Jorge; Junquera, Javier

    Symmetry breaking at ferroelectric domain walls gives rise to new physical properties, offering the opportunity to use the domain walls themselves as a functional separate object in a device. One example is the appearance of an enhanced conductivity at the boundaries between ferroelectric domains in oxides. A realistic first-principles simulation of the domains walls is limited to highly-symmetric cleanly-cut walls in order to keep the number of atoms in the simulation box small. Here we use a recently developed second-principles method that treats all the lattice degrees of freedom and the relevant electronic ones on the same foot with high accuracy at a modest computational cost. We apply it to the demading physical problem of head-to-head (HH) and tail-to-tail (TT) domain walls in ferroelectric PbTiO3 thin films. These interfaces present a large and unfavourable electrostatic energy due to the polarization-induced bound charge at the domain wall. An accurate simulation should capture eventual charge transfers between the walls, and the concomitant electron-lattice coupling. We show how the polarization discontinuity in HH and TT domain walls in PbTiO3 thin films can be effectively screened by the formation of two-dimensional electron gases of electrons and holes. Finantial support from MINECO Grant No. FIS2012-37549-C05-04.

  4. Head-to-head comparison of protocol modifications for the generation of collagen-induced arthritis in a specific-pathogen free facility using DBA/1 mice.

    PubMed

    Thornton, Sherry; Strait, Richard T

    2016-01-01

    Collagen-induced arthritis (CIA) is a widely used mouse model for studying inflammatory arthritis (IA). However, CIA induction protocols differ between laboratories, and direct comparison between protocol variations has not been reported. To address this issue, DBA/1 mice housed in conventional and specific-pathogen free (SPF) facilities were administered various combinations of two doses of collagen type II (CII) in complete (CFA) or incomplete Freund's adjuvant (IFA); some mice were also injected with lipopolysaccharide (LPS) and/or additional CII at specific intervals. Mice were evaluated for IA over the subsequent 2 months. Depending directly on the combination of CII, CFA, IFA, and LPS used, the incidence of IA ranged between 20%-100%, and severity extended from mild to severe even in an SPF environment. Our results demonstrate for the first time in head-to-head comparisons that specific variations in the use of CII, CFA, IFA, and LPS can induce a range of arthritic disease intensity and severity in an SPF facility. Thus, distinct experimental settings can be designed for robust assessment of factors that either exacerbate or inhibit arthritis pathogenesis. Furthermore, by achieving 100% incidence in an SPF facility, the protocols provide a practical and humane benefit by reducing the number of mice necessary for experimental assessment. PMID:26956089

  5. Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania.

    PubMed

    Todolí, Felicitat; Rodríguez-Cortés, Alhelí; Núñez, María Del Carmen; Laurenti, Márcia D; Gómez-Sebastián, Silvia; Rodríguez, Fernando; Pérez-Martín, Eva; Escribano, José M; Alberola, Jordi

    2012-01-01

    Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines- is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against

  6. Pharmacoeconomic comparison of aripiprazole once-monthly and paliperidone palmitate from a head-to-head clinical trial in schizophrenia: a US analysis

    PubMed Central

    Sapin, Christophe; Hartry, Ann; Kamat, Siddhesh A.; Beillat, Maud; Baker, Ross A.; Eramo, Anna

    2016-01-01

    Schizophrenia presents a substantial clinical and economic burden to the health-care system. In QUAlity of LIfe with AbiliFY Maintena (QUALIFY), a randomized head-to-head study of aripiprazole once-monthly 400 mg (AOM 400) compared with paliperidone palmitate (PP; 78–234 mg/mo), AOM 400 demonstrated greater improvement in health-related quality of life and functioning in patients with stable schizophrenia. The present analysis used health economics assessment data collected during the QUALIFY study to determine the direct medical and pharmacy costs and the cost-effectiveness associated with each treatment over 6 months. Compared with those receiving PP, patients receiving AOM 400 incurred significantly lower direct total costs ($8908±186 vs $9675±190, p=0.005) and treatment costs ($7967±113 vs $8706±116, p<0.001). Effectiveness results in the subset of patients included in the cost analyses were similar to the overall population: mean (95% CI) improvement in Heinrichs-Carpenter Quality of Life Scale total score was greater with AOM 400 (5.97 [3.87; 8.08]) compared with PP (2.85 [0.56; 5.08]). Likewise, Clinical Global Impression–Severity improved more in the AOM 400 group (−0.59 [−0.71; −0.47]) compared with PP group (−0.37 [−0.46; −0.27]). Therefore, the analysis of data from stabilized patients with schizophrenia in the QUALIFY study indicated that AOM 400 is associated with lower health-care costs and greater effectiveness compared with PP and thus represents the economically dominant strategy. PMID:27708677

  7. Head-to-Head Comparison of Three Vaccination Strategies Based on DNA and Raw Insect-Derived Recombinant Proteins against Leishmania

    PubMed Central

    Núñez, María del Carmen; Laurenti, Márcia D.; Gómez-Sebastián, Silvia; Rodríguez, Fernando; Pérez-Martín, Eva; Escribano, José M.

    2012-01-01

    Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories –the cheapest way of producing DNA-PROT vaccines– is a practical and cost-effective way for potential “off the shelf” supplying vaccines at very low prices for the protection against

  8. A head-to-head randomized clinical trial of methylphenidate and atomoxetine treatment for executive function in adults with attention-deficit hyperactivity disorder.

    PubMed

    Ni, Hsing-Chang; Shang, Chi-Yung; Gau, Susan Shur-Fen; Lin, Yu-Ju; Huang, Hui-Chun; Yang, Li-Kuang

    2013-10-01

    Results regarding the effects of methylphenidate and atomoxetine on executive functions were inconsistent and no study has directly compared the efficacy of these two medications in improving executive functions in adults with attention-deficit hyperactivity disorder (ADHD). We conducted an 8-10 wk, open-label, head-to-head, randomized clinical trial involving adults with a clinical diagnosis of ADHD confirmed by psychiatric interview. The two treatment arms were immediate-release methylphenidate (IR-methylphenidate) (n = 31) and atomoxetine once daily (n = 32). Executive functions were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), including spatial working memory, spatial span, intra-extra dimensional set shifts, rapid visual information processing and Stockings of Cambridge (SOC). In addition to the symptom assessments at baseline (week 0), visit 2 (week 4-5) and visit 3 (week 8–10), they received CANTAB assessments at baseline and visit 3 (60.4 ± 6.3 d). Compared to baseline, adults treated with atomoxetine showed significant improvement in spatial working memory, spatial short-term memory, sustained attention and spatial planning at visit 3; adults treated with IR-methylphenidate showed significant improvement in spatial working memory at visit 3. Comparing the magnitude of improvement in executive functions between these two medications, the effect was generally similar for the two groups, although atomoxetine might have significantly greater efficacy than IR-methylphenidate in terms of improving spatial planning (SOC). Our results provide evidence to support that both IR-methylphenidate and atomoxetine improved various executive functions in adults with ADHD with greater improvement in atomoxetine than IR-methylphenidate in spatial planning.

  9. Low Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James

    2002-09-14

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation.

  10. Radiation Leukemogenesis at Low Dose Rates

    SciTech Connect

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  11. Tardive dyskinesia with low dose amisulpride.

    PubMed

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

  12. Low Dose Effects: Benefit or Harm?

    PubMed

    Woloschak, Gayle E

    2016-03-01

    This forum article discusses issues related to the effects of low dose radiation, an area that is under intense study but difficult to assess. Experiments with large-scale animal studies are included in this paper; these studies point to the need for international consortia to examine and balance the results of these large-scale studies and databases. PMID:26808889

  13. Epigenomic Adaptation to Low Dose Radiation

    SciTech Connect

    Gould, Michael N.

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  14. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  15. The Efficacy of Natalizumab versus Fingolimod for Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review, Indirect Evidence from Randomized Placebo-Controlled Trials and Meta-Analysis of Observational Head-to-Head Trials

    PubMed Central

    Tsivgoulis, Georgios; Katsanos, Aristeidis H.; Mavridis, Dimitris; Grigoriadis, Nikolaos; Dardiotis, Efthymios; Heliopoulos, Ioannis; Papathanasopoulos, Panagiotis; Karapanayiotides, Theodoros; Kilidireas, Constantinos; Hadjigeorgiou, Georgios M.; Voumvourakis, Konstantinos

    2016-01-01

    Background Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation. PMID:27684943

  16. [Low dose naltrexone for treatment of pain].

    PubMed

    Plesner, Karin Bruun; Vægter, Henrik Bjarke; Handberg, Gitte

    2015-10-01

    Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy. PMID:26509454

  17. 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

  18. Low-dose radiation exposure and carcinogenesis.

    PubMed

    Suzuki, Keiji; Yamashita, Shunichi

    2012-07-01

    Absorption of energy from ionizing radiation by the genetic material in the cell leads to damage to DNA, which in turn leads to cell death, chromosome aberrations and gene mutations. While early or deterministic effects result from organ and tissue damage caused by cell killing, latter two are considered to be involved in the initial events that lead to the development of cancer. Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear energy transfer radiation. A linear, no-threshold model has been applied to assessment of the risks resulting from exposure to moderate and high doses of ionizing radiation; however, a statistically significant increase has hardly been described for radiation doses below 100 mSv. This review summarizes our current knowledge of the physical and biological features of low-dose radiation and discusses the possibilities of induction of cancer by low-dose radiation. PMID:22641644

  19. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

    Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

  20. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  1. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  2. Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al; Buchner, Stephen; LaBel, Kenneth

    2011-01-01

    We have presented results of ultra-low dose rate irradiations (< or = 10 mrad(Si)/s) for a variety of radiation hardened and commercial linear bipolar devices. We observed low dose rate enhancement factors exceeding 1.5 in several parts. The worst case of dose rate enhancement resulted in functional failures, which occurred after 10 and 60 krad(Si), for devices irradiated at 0.5 and 10 mrad(Si)/s, respectively. Devices fabricated with radiation hardened processes and designs also displayed dose rate enhancement at below 10 mrad(Si)/s. Furthermore, the data indicated that these devices have not reached the damage saturation point. Therefore the degradation will likely continue to increase with increasing total dose, and the low dose rate enhancement will further magnify. The cases presented here, in addition to previous examples, illustrate the significance and pervasiveness of low dose rate enhancement at dose rates lower than 10 mrad(Si). These results present further challenges for radiation hardness assurance of bipolar linear circuits, and raise the question of whether the current standard test dose rate is conservative enough to bound degradations due to ELDRS.

  3. Low-dose computed tomography image restoration using previous normal-dose scan

    SciTech Connect

    Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

    2011-10-15

    Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

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

    SciTech Connect

    Scott, Bobby, R., Ph.D.

    2003-06-27

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

  5. The CaTin1 (Capsicum annuum TMV-induced clone 1) and CaTin1-2 genes are linked head-to-head and share a bidirectional promoter.

    PubMed

    Shin, Ryoung; Kim, Min Jung; Paek, Kyung-Hee

    2003-05-01

    CaTin1 was expressed relatively early in the TMV-inoculated leaves of hot pepper which is resistant to TMV-P(0) infection. Interestingly, there was another homologous gene (CaTin1-2) located in front of CaTin1 in a head-to-head fashion and they shared a single promoter. The expression profile of the CaTin1-2 was very similar to CaTin1 in all the treatments except the slower induction time compared to CaTin1 upon TMV-P(0) inoculation. The promoter analysis of CaTin1 and CaTin1-2 revealed bidirectionality both in cis-elements and activity. The CaTin1-2 promoter had two TATA-boxes, four GCC-boxes, the root responsive element, and a W1-box. The ethylene-inducible promoter activity depended on GCC-boxes and TMV-inducible activity of the CaTin1-2 promoter reached its highest activity when this promoter had a W1-box.

  6. Head-to-Head Comparison of Ultra-High-Performance Liquid Chromatography with Diode Array Detection versus Quantitative Nuclear Magnetic Resonance for the Quantitative Analysis of the Silymarin Complex in Silybum marianum Fruit Extracts.

    PubMed

    Cheilari, Antigoni; Sturm, Sonja; Intelmann, Daniel; Seger, Christoph; Stuppner, Hermann

    2016-02-24

    Quantitative nuclear magnetic resonance (qNMR) spectroscopy is known as an excellent alternative to chromatography-based mixture analysis. NMR spectroscopy is a non-destructive method, needs only limited sample preparation, and can be readily automated. A head-to-head comparison of qNMR to an ultra-high-performance liquid chromatography with diode array detection (uHPLC-DAD)-based quantitative analysis of six flavonolignan congeners (silychristin, silydianin, silybin A, silybin B, isosilybin A, and isosilybin B) of the Silybum marianum silymarin complex is presented. Both assays showed similar performance characteristics (linear range, accuracy, precision, and limits of quantitation) with analysis times below 30 min/sample. The assays were applied to industrial S. marianum extracts (AC samples) and to extracts locally prepared from S. marianum fruits (PL samples). An assay comparison by Bland-Altman plots (relative method bias AC samples, -0.1%; 2SD range, ±5.1%; relative method bias PL samples, -0.3%; 2SD range, ±7.8%) and Passing-Bablok regression analysis (slope and intercept for AC and PL samples not significantly different from 1.00 and 0.00, respectively; Spearman's coefficient of rank correlation, >0.99) did show that qNMR and uHPLC-DAD can be used interchangeably to quantitate flavonolignans in the silymarin complex.

  7. Low-dose effects of hormones and endocrine disruptors.

    PubMed

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately.

  8. Evaluation of a head-to-head study of lisdexamfetamine dimesylate and atomoxetine: evaluation of Dittmann RW, Cardo E, Nagy P, et al. Efficacy and safety of lisdexamfetamine dimesylate and atomoxetine in the treatment of attention-deficit/hyperactivity disorder: a head-to-head, randomised, double-blind, Phase IIIb study. CNS Drugs 2013;27:1081-1092. doi: 10.1007/s40263-013-0104-8 ClinicalTrials.gov: NCT01106430.

    PubMed

    Banaschewski, Tobias; Rothermel, Boris; Poustka, Luise

    2014-09-01

    Here, we evaluate a report of a head-to-head study of the prodrug stimulant lisdexamfetamine dimesylate (LDX) and the non-stimulant atomoxetine hydrochloride (ATX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). An inadequate response to previous methylphenidate (MPH) treatment was a notable inclusion criterion. The primary efficacy outcome of a more rapid clinical response to LDX than to ATX was predictable from the known properties of the two drugs. However, secondary efficacy outcomes indicated that LDX was significantly more effective than ATX in relieving investigator-rated symptoms of ADHD, with an effect size of 0.56. Safety and tolerability profiles were consistent with the known properties of LDX and ATX. Despite some issues with the study design, the conclusion that LDX is more effective than ATX over the short term appears robust. In addition, the magnitude of improvement with both treatments indicated that previous MPH treatment is not a factor affecting the potential for patients to benefit from LDX or ATX. The results may help to inform clinical practice in Europe, where LDX is approved for treating children and adolescents with ADHD and a previous inadequate response to MPH, and in other regions where generic MPH formulations are typically the first-line therapeutic option.

  9. Validation of true low-dose 18F-FDG PET of the brain

    PubMed Central

    Fällmar, David; Lilja, Johan; Kilander, Lena; Danfors, Torsten; Lubberink, Mark; Larsson, Elna-Marie; Sörensen, Jens

    2016-01-01

    The dosage of 18F-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n=17) underwent FDG-PET/CT twice on separate occasions, first with normal-dose (3 MBq/kg), and second with low-dose (0.75 MBq/kg, 25% of the original). Five additional controls (total n=22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal- and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children. PMID:27766185

  10. The genes for the alpha 1(IV) and alpha 2(IV) chains of human basement membrane collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure.

    PubMed Central

    Pöschl, E; Pollner, R; Kühn, K

    1988-01-01

    The human basement membrane specific collagen type IV is a heterotrimer composed of two alpha 1(IV) chains and one alpha 2(IV) chain. A partial genomic EcoRI library was screened with cDNA clones representing the 5' end regions of the alpha 1(IV) and the alpha 2(IV) mRNA. A 2.2-kb genomic fragment was isolated and sequenced, which contains the 5' terminal exons of both genes located in close vicinity. The two genes were found to be arranged in opposite direction, head-to-head, separated only by a short region of 127 bp, apparently representing promoters of both genes as indicated by the existence of typical sequence motifs (CAT-box, SP1 consensus sequence). These data suggest that the alpha 1(IV) and alpha 2(IV) genes use a common, bidirectional promoter. The striking symmetrical arrangement of sequence elements within the promoter may be of basic importance for the coordination of bidirectional transcription. The promoter region had no detectable transcriptional activity in transient gene expression assays after fusion to the chloramphenicol acetylase (CAT) gene in either direction, indicating the necessity of additional elements for efficient and tissue-specific expression of both genes. Constructs containing different segments of both genes failed to identify regions with enhancing activity for the homologous collagen type IV promoter. When the heterologous HSV thymidine kinase promoter was used, a negatively acting region was identified. This indicates that the alpha 1(IV) and alpha 2(IV) promoter activity is controlled by additional regulatory elements present on distant portions of both genes. Images PMID:2846280

  11. Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate.

    PubMed

    Nagy, Peter; Häge, Alexander; Coghill, David R; Caballero, Beatriz; Adeyi, Ben; Anderson, Colleen S; Sikirica, Vanja; Cardo, Esther

    2016-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.

  12. Quantification of Adaptive Protection Following Low-dose Irradiation.

    PubMed

    Feinendegen, Ludwig E

    2016-03-01

    The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge. PMID:26808882

  13. Risk of cancer subsequent to low-dose radiation

    SciTech Connect

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident. (PCS)

  14. Low-Dose Hyper-Radiosensitivity: Past, Present, and Future

    SciTech Connect

    Marples, Brian Collis, Spencer J.

    2008-04-01

    This review article discusses the biology of low-dose hyper-radiosensitivity (HRS) with reference to the molecular regulation of DNA repair and cell cycle control processes. Particular attention is paid to the significance of G2-phase cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity and the impact of HRS on low-dose rate radiobiology. The history of HRS from the original in vivo discovery to the most recent in vitro and clinical data are examined to present a unifying hypothesis concerning the molecular control and regulation of this important low dose radiation response. Finally, preclinical and clinical data are discussed, from a molecular viewpoint, to provide theoretical approaches to exploit HRS biology for clinical gain.

  15. Response of Biological Systems to Low Doses of Ionizing Radiation.

    PubMed

    Hei, Tom K

    2016-03-01

    Radiation is ubiquitous in the environment. Biological effects of exposure to low doses of ionizing radiation are subjected to several modulating factors. Two of these, bystander response and adaptive protections, are discussed briefly. PMID:26808883

  16. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  17. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    PubMed Central

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  18. Low-Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James; Slovic, Paul

    2001-06-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email & internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals.

  19. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes.

  20. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes. PMID:19820457

  1. High-resolution low-dose scanning transmission electron microscopy

    PubMed Central

    Buban, James P.; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D.; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM. PMID:19915208

  2. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  3. Learned Shrinkage Approach for Low-Dose Reconstruction in Computed Tomography

    PubMed Central

    Zibulevsky, Michael

    2013-01-01

    We propose a direct nonlinear reconstruction algorithm for Computed Tomography (CT), designed to handle low-dose measurements. It involves the filtered back-projection and adaptive nonlinear filtering in both the projection and the image domains. The filter is an extension of the learned shrinkage method by Hel-Or and Shaked to the case of indirect observations. The shrinkage functions are learned using a training set of reference CT images. The optimization is performed with respect to an error functional in the image domain that combines the mean square error with a gradient-based penalty, promoting image sharpness. Our numerical simulations indicate that the proposed algorithm can manage well with noisy measurements, allowing a dose reduction by a factor of 4, while reducing noise and streak artifacts in the FBP reconstruction, comparable to the performance of a statistically based iterative algorithm. PMID:23864851

  4. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    EPA Science Inventory

    Carcinogenic Effects of Low Doses of Ionizing Radiation

    R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    The form of the dose-response curve for radiation-induced cancers, particu...

  5. Malignant melanoma of the tongue following low-dose radiation

    SciTech Connect

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  6. Systemic response to low-dose endotoxin infusion in cats.

    PubMed

    DeClue, Amy E; Williams, Kurt J; Sharp, Claire; Haak, Carol; Lechner, Elizabeth; Reinero, Carol R

    2009-12-15

    Sepsis is a common problem in feline patients and is associated with substantial morbidity and mortality. There has been little research investigating the physiologic response to bacterial infection in cats, in part because appropriate models have not been developed. The objective of this study was to characterize the response to low-dose LPS infusion in conscious, healthy cats. Measures of systemic inflammation, hemodynamic stability, coagulation, metabolic function, and organ damage were compared between placebo and low-dose LPS infusion (2mcg/kg/hx4h, IV) in cats, with each cat serving as its own control. Markers of systemic inflammation including temperature, plasma TNF activity, IL-6, CXCL-8 and IL-10 concentrations were significantly increased and white blood cell counts were significantly decreased after LPS infusion. A biphasic hypotensive response was observed after initiation of LPS infusion without concurrent tachycardia. Additionally, LPS administration significantly increased blood glucose, lactate and creatinine concentrations. Patchy alveolar congestion, multifocal acute alveolar epithelial necrosis, and mild pulmonary edema were noted in the lungs along with acute centrilobular hepatocellular necrosis, and mild lymphocyte apoptosis in the spleen and/or intestinal Peyer's patches. No biologically significant alterations in coagulation parameters developed after LPS infusion. Low-dose LPS infusion in cats induced systemic inflammation, hemodynamic derangement, metabolic alterations and mild organ damage. Low-dose endotoxin infusion is a viable pre-clinical model to study naturally developing sepsis in cats.

  7. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    SciTech Connect

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  8. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications.

  9. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications. PMID:27621948

  10. Organ Dose and Attributable Cancer Risk in Lung Cancer Screening with Low-Dose Computed Tomography

    PubMed Central

    Saltybaeva, Natalia; Martini, Katharina; Frauenfelder, Thomas; Alkadhi, Hatem

    2016-01-01

    Purpose Lung cancer screening with CT has been recently recommended for decreasing lung cancer mortality. The radiation dose of CT, however, must be kept as low as reasonably achievable for reducing potential stochastic risks from ionizing radiation. The purpose of this study was to calculate individual patients’ lung doses and to estimate cancer risks in low-dose CT (LDCT) in comparison with a standard dose CT (SDCT) protocol. Materials and Methods This study included 47 adult patients (mean age 63.0 ± 5.7 years) undergoing chest CT on a third-generation dual-source scanner. 23/47 patients (49%) had a non-enhanced chest SDCT, 24 patients (51%) underwent LDCT at 100 kVp with spectral shaping at a dose equivalent to a chest x-ray. 3D-dose distributions were obtained from Monte Carlo simulations for each patient, taking into account their body size and individual CT protocol. Based on the dose distributions, patient-specific lung doses were calculated and relative cancer risk was estimated according to BEIR VII recommendations. Results As compared to SDCT, the LDCT protocol allowed for significant organ dose and cancer risk reductions (p<0.001). On average, lung dose was reduced from 7.7 mGy to 0.3 mGy when using LDCT, which was associated with lowering of the cancer risk from 8.6 to 0.35 per 100’000 cases. A strong linear correlation between lung dose and patient effective diameter was found for both protocols (R2 = 0.72 and R2 = 0.75 for SDCT and LDCT, respectively). Conclusion Use of a LDCT protocol for chest CT with a dose equivalent to a chest x-ray allows for significant lung dose and cancer risk reduction from ionizing radiation. PMID:27203720

  11. Investigation of lung nodule detectability in low-dose 320-slice computed tomography

    SciTech Connect

    Silverman, J. D.; Paul, N. S.; Siewerdsen, J. H.

    2009-05-15

    Low-dose imaging protocols in chest CT are important in the screening and surveillance of suspicious and indeterminate lung nodules. Techniques that maintain nodule detectability yet permit dose reduction, particularly for large body habitus, were investigated. The objective of this study was to determine the extent to which radiation dose can be minimized while maintaining diagnostic performance through knowledgeable selection of reconstruction techniques. A 320-slice volumetric CT scanner (Aquilion ONE, Toshiba Medical Systems) was used to scan an anthropomorphic phantom at doses ranging from {approx}0.1 mGy up to that typical of low-dose CT (LDCT, {approx}5 mGy) and diagnostic CT ({approx}10 mGy). Radiation dose was measured via Farmer chamber and MOSFET dosimetry. The phantom presented simulated nodules of varying size and contrast within a heterogeneous background, and chest thickness was varied through addition of tissue-equivalent bolus about the chest. Detectability of a small solid lung nodule (3.2 mm diameter, -37 HU, typically the smallest nodule of clinical significance in screening and surveillance) was evaluated as a function of dose, patient size, reconstruction filter, and slice thickness by means of nine-alternative forced-choice (9AFC) observer tests to quantify nodule detectability. For a given reconstruction filter, nodule detectability decreased sharply below a threshold dose level due to increased image noise, especially for large body size. However, nodule detectability could be maintained at lower doses through knowledgeable selection of (smoother) reconstruction filters. For large body habitus, optimal filter selection reduced the dose required for nodule detection by up to a factor of {approx}3 (from {approx}3.3 mGy for sharp filters to {approx}1.0 mGy for the optimal filter). The results indicate that radiation dose can be reduced below the current low-dose (5 mGy) and ultralow-dose (1 mGy) levels with knowledgeable selection of

  12. Standardization and Optimization of Computed Tomography Protocols to Achieve Low-Dose

    PubMed Central

    Chin, Cynthia; Cody, Dianna D.; Gupta, Rajiv; Hess, Christopher P.; Kalra, Mannudeep K.; Kofler, James M.; Krishnam, Mayil S.; Einstein, Andrew J.

    2014-01-01

    The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities and various indications require unique protocols, but there remains room for standardization and optimization. In this paper we summarize approaches to reduce dose, as discussed in lectures comprising the first session of the 2013 UCSF Virtual Symposium on Radiation Safety in Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing-tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose. PMID:24589403

  13. SU-F-18C-15: Model-Based Multiscale Noise Reduction On Low Dose Cone Beam Projection

    SciTech Connect

    Yao, W; Farr, J

    2014-06-15

    Purpose: To improve image quality of low dose cone beam CT for patient positioning in radiation therapy. Methods: In low dose cone beam CT (CBCT) imaging systems, Poisson process governs the randomness of photon fluence at x-ray source and the detector because of the independent binomial process of photon absorption in medium. On a CBCT projection, the variance of fluence consists of the variance of noiseless imaging structure and that of Poisson noise, which is proportional to the mean (noiseless) of the fluence at the detector. This requires multiscale filters to smoothen noise while keeping the structure information of the imaged object. We used a mathematical model of Poisson process to design multiscale filters and established the balance of noise correction and structure blurring. The algorithm was checked with low dose kilo-voltage CBCT projections acquired from a Varian OBI system. Results: From the investigation of low dose CBCT of a Catphan phantom and patients, it showed that our model-based multiscale technique could efficiently reduce noise and meanwhile keep the fine structure of the imaged object. After the image processing, the number of visible line pairs in Catphan phantom scanned with 4 ms pulse time was similar to that scanned with 32 ms, and soft tissue structure from simulated 4 ms patient head-and-neck images was also comparable with scanned 20 ms ones. Compared with fixed-scale technique, the image quality from multiscale one was improved. Conclusion: Use of projection-specific multiscale filters can reach better balance on noise reduction and structure information loss. The image quality of low dose CBCT can be improved by using multiscale filters.

  14. Sheet Resistance Low Dose Monitoring Using The Double Implant Technique

    NASA Astrophysics Data System (ADS)

    Smith, A. K.; Johnson, W. H.; Keenan, W. A.

    1986-06-01

    Sheet resistance has become an industry standard for monitoring high and medium dose ion implants. For low dose there are two sheet resistance techniques available, the direct implant technique and the double implant technique. Careful processing has extended the range of direct sheet resistance measurements down to doses of 2E11 ions/cm2. The double implant technique requires an initial implant to create an easily measured sheet resistance layer that serves as the test vehicle for the second implant. The dose of the second implant is measured by monitoring the change in the sheet resistance due to the implant damage created by the second implant into the first. This double implant technique is not limited to low dose nor to species that are electrically active in the substrate.

  15. Patient release criteria for low dose rate brachytherapy implants.

    PubMed

    Boyce, Dale E; Sheetz, Michael A

    2013-04-01

    A lack of consensus regarding a model governing the release of patients following sealed source brachytherapy has led to a set of patient release policies that vary from institution to institution. The U.S. Nuclear Regulatory Commission has issued regulatory guidance on patient release in NUREG 1556, Volume 9, Rev. 2, Appendix U, which allows calculation of release limits following implant brachytherapy. While the formalism presented in NUREG is meaningful for the calculation of release limits in the context of relatively high energy gamma emitters, it does not estimate accurately the effective dose equivalent for the common low dose rate brachytherapy sources Cs, I, and Pd. NUREG 1556 states that patient release may be based on patient-specific calculations as long as the calculation is documented. This work is intended to provide a format for patient-specific calculations to be used for the consideration of patients' release following the implantation of certain low dose rate brachytherapy isotopes. PMID:23439145

  16. Etched track detectors and the low dose problem.

    PubMed

    Pálfalvi, J; Dám, A M; Bogdándi, E N; Polonyi, I; Szabó, J; Balásházy, I; Farkas, A

    2003-01-01

    The risk to human health of exposure to low-level radiation is not precisely known yet. One way of studying this is to carry out in vitro biological experiments with cell cultures and to extend the conclusions to biological models. To relate the macroscopically deteminable 'low dose' to the damage of cells caused by a certain type of ionising particle is nearly impossible. therefore the number of hits and the imparted energy are the significant quantities. They can be estimated by particle transport calculations and by direct measurements. The effect of low dose was investigated in radio-adaptation experiments when mono-layers of different unsynchronised cell cultures were irradiated by neutrons produced in the filtered beam of the Budapest Research Reactor (BRR). The energy deposition was investigated by replacing the mono-layers with etched track detectors of the CR-39 type. PMID:12678384

  17. Role of animal studies in low-dose extrapolation

    SciTech Connect

    Fry, R.J.M.

    1981-01-01

    Current data indicate that in the case of low-LET radiation linear, extrapolation from data obtained at high doses appears to overestimate the risk at low doses to a varying degree. In the case of high-LET radiation, extrapolation from data obtained at doses as low as 40 rad (0.4 Gy) is inappropriate and likely to result in an underestimate of the risk.

  18. Responses of astrocytes in culture after low dose laser irradiation

    SciTech Connect

    Yew, D.T.; Zheng, D.R.; Au, C.; Li, W.W. )

    1990-03-01

    The effect of Helium-Neon low dose laser on astrocytes was investigated in cultures of isolated astrocytes from albino neonatal rats. The laser appeared to inhibit the growth of astrocytes as exemplified by the smaller sizes of the cells and the decreased leucine uptake in each cell after treatment. Temporary decrease in the number of mitoses was also observed, but this trend was reversed soon after. Electron microscopic studies revealed an increase in buddings from cell bodies and processes (branches) after irradiation.

  19. Analysis of low-dose radiation shield effectiveness of multi-gate polymeric sheets

    NASA Astrophysics Data System (ADS)

    Kim, S. C.; Lee, H. K.; Cho, J. H.

    2014-07-01

    Computed tomography (CT) uses a high dose of radiation to create images of the body. As patients are exposed to radiation during a CT scan, the use of shielding materials becomes essential in CT scanning. This study was focused on the radiation shielding materials used for patients during a CT scan. In this study, sheets were manufactured to shield the eyes and the thyroid, the most sensitive parts of the body, against radiation exposure during a CT scan. These sheets are manufactured using silicone polymers, barium sulfate (BaSO4) and tungsten, with the aim of making these sheets equally or more effective in radiation shielding and more cost-effective than lead sheets. The use of barium sulfate drew more attention than tungsten due to its higher cost-effectiveness. The barium sulfate sheets were coated to form a multigate structure by applying the maximum charge rate during the agitator and subsequent mixing processes and creating multilayered structures on the surface. To measure radiation shielding effectiveness, the radiation dose was measured around both eyes and the thyroid gland using sheets in three different thicknesses (1, 2 and 3 mm). Among the 1 and 2 mm sheets, the Pb sheets exhibited greater effectiveness in radiation shielding around both eyes, but the W sheets were more effective in radiation shielding around the thyroid gland. In the 3 mm sheets, the Pb sheet also attenuated a higher amount of radiation around both eyes while the W sheet was more effective around the thyroid gland. In conclusion, the sheets made from barium sulfate and tungsten proved highly effective in shielding against low-dose radiation in CT scans without causing ill-health effects, unlike lead.

  20. Screening for lung cancer using low dose computed tomography.

    PubMed

    Tammemagi, Martin C; Lam, Stephen

    2014-01-01

    Screening for lung cancer with low dose computed tomography can reduce mortality from the disease by 20% in high risk smokers. This review covers the state of the art knowledge on several aspects of implementing a screening program. The most important are to identify people who are at high enough risk to warrant screening and the appropriate management of lung nodules found at screening. An accurate risk prediction model is more efficient than age and pack years of smoking alone at identifying those who will develop lung cancer and die from the disease. Algorithms are available for assessing people who screen positive to determine who needs additional imaging or invasive investigations. Concerns about low dose computed tomography screening include false positive results, overdiagnosis, radiation exposure, and costs. Further work is needed to define the frequency and duration of screening and to refine risk prediction models so that they can be used to assess the risk of lung cancer in special populations. Another important area is the use of computer vision software tools to facilitate high throughput interpretation of low dose computed tomography images so that costs can be reduced and the consistency of scan interpretation can be improved. Sufficient data are available to support the implementation of screening programs at the population level in stages that can be expanded when found to perform well to improve the outcome of patients with lung cancer. PMID:24865600

  1. Low dose monitors — the movements and causes

    NASA Astrophysics Data System (ADS)

    Cherekdjian, S.

    1993-04-01

    A previous paper [Nucl. Instr. and Meth. B55 (1991) 178] has demonstrated that the correct equipment specification and process procedures enable the reliable direct probing of low dose sheet resistance monitors. Utilizing this, we are able to characterize the instability of low dose monitors to process and ambient conditions. Several experiments are conducted to determine the origin of the movements. These movements were found to be either "short term", or "long term". The former is a result of the interaction of the wafer and its processing prior to measurement. While the latter is a slow change after processing. The correct specification of the wafers, wafer processing, and the condition of the four point probe tips enable the low dose measurement to be performed. The value of the initial result, "short term movement", is shown to be directly the consequence of wet chemistry and the ambient anneal condition. While the stability of the wafer after measurement, "long term movement", is found to be the electrical degradation of the surface of the silicon. A key factor in this stability problem is the exposure of the wafer to air, especially to moisture in the atmosphere. X-ray photo spectroscopy (XPS), and time of flight secondary ion mass Spectrometry (TOP SIMS) results give an insight to the complexity of the surface condition. These range from oxide growth, surface chemistry, and hydrogen injection.

  2. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis. PMID:25355191

  3. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    SciTech Connect

    Schoenfeld, Gordon O.; Amdur, Robert J. . E-mail: amdurrj@ufl.edu; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-06-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

  4. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  5. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    PubMed Central

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    venlafaxine; p=0.09). Treatment satisfaction was highest (69%) on estradiol (p<0.001 versus placebo), lowest (39%) on placebo, and intermediate (52%) for venlafaxine (p=0.06 versus placebo). Both interventions were well tolerated. Conclusions Low-dose oral estradiol and venlafaxine are both effective treatments for vasomotor symptoms in midlife women. While efficacy of low-dose estradiol may be slightly superior to that of venlafaxine, the difference is small in magnitude and of uncertain clinical relevance. Clinicaltrials.gov identifier NCT01418209, http://clinicaltrials.gov/ct2/show/NCT01418209?term=NCT01418209&rank=1 PMID:24861828

  6. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  7. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no

  8. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?

    SciTech Connect

    Snow, Elizabeth T. . E-mail: esnow@deakin.edu.au; Sykora, Peter; Durham, Troy R.; Klein, Catherine B.

    2005-09-01

    Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to {<=}60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 {mu}M arsenite (As{sup III}) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase {beta} and DNA ligase I. At higher concentrations (> 10 {mu}M), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

  9. High or low dose radioiodine ablation of thyroid remnants?

    PubMed

    Creutzig, H

    1987-01-01

    The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3569338

  10. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  11. Measurement uncertainty analysis of low-dose-rate prostate seed brachytherapy: post-implant dosimetry.

    PubMed

    Gregory, Kent J; Pattison, John E; Bibbo, Giovanni

    2015-03-01

    The minimal dose covering 90 % of the prostate volume--D 90--is arguably the most important dosimetric parameter in low-dose-rate prostate seed brachytherapy. In this study an analysis of the measurement uncertainties in D 90 from low-dose-rate prostate seed brachytherapy was conducted for two common treatment procedures with two different post-implant dosimetry methods. The analysis was undertaken in order to determine the magnitude of D 90 uncertainty, how the magnitude of the uncertainty varied when D 90 was calculated using different dosimetry methods, and which factors were the major contributors to the uncertainty. The analysis considered the prostate as being homogeneous and tissue equivalent and made use of published data, as well as original data collected specifically for this analysis, and was performed according to the Guide to the expression of uncertainty in measurement (GUM). It was found that when prostate imaging and seed implantation were conducted in two separate sessions using only CT images for post-implant analysis, the expanded uncertainty in D 90 values were about 25 % at the 95 % confidence interval. When prostate imaging and seed implantation were conducted during a single session using CT and ultrasound images for post-implant analysis, the expanded uncertainty in D 90 values were about 33 %. Methods for reducing these uncertainty levels are discussed. It was found that variations in contouring the target tissue made the largest contribution to D 90 uncertainty, while the uncertainty in seed source strength made only a small contribution. It is important that clinicians appreciate the overall magnitude of D 90 uncertainty and understand the factors that affect it so that clinical decisions are soundly based, and resources are appropriately allocated.

  12. Extrapyramidal side effects with low doses of amisulpride.

    PubMed

    Mandal, Nikhiles; Singh, Om P; Sen, Subrata

    2014-04-01

    Amisulpride, the newly introduced antipsychotic in India, is claimed to be effective in both positive and negative symptom schizophrenia and related disorders, though it has little or no action on serotonergic receptors. Limbic selectivity and lower striatal dopaminergic receptor binding capacity causes very low incidence of EPS. But, in clinical practice, we are getting EPS with this drug even at lower doses. We have reported three cases of akathisia, acute dystonia, and drug-induced Parkinsonism with low doses of amisulpride. So, we should keep this side effect in mind when using amisulpride. In fact, more studies are required in our country to find out the incidence of EPS and other associated mechanism.

  13. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

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

    2016-05-01

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

  14. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

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

    2016-05-01

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

  15. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    SciTech Connect

    Yuan, Zhi-Min

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  16. Low-dose Computed Tomography in a Pregnant Woman with a Ruptured Pseudoaneurysm of the Abdominal Aorta.

    PubMed

    Ramac, Jelena Popić; Vidjak, Vinko; Skegro, Dinko; Duić, Zeljko; Blasković, Darko; Erdelez, Lidija; Skopljanac-Macina, Andrija; Suknaić, Slaven; Slavica, Marko; Leder, Nikola Ivan

    2015-09-01

    Imaging the pregnant patient presents a unique challenge to radiologist due to the risk of radiation to the conceptus (embryo/fetus). A rare case of a successfully recognized and treated pseudoaneurysm (PA) of the abdominal aorta is to be presented. The pseudoaneurysm occurred in the third trimester and had a favorable outcome for the mother and the baby. Emergent abdominal ultrasound (US) is the first modality in diagnostic algorithm for the rupture of aortic aneurysm in a pregnant woman. It provides the most rapid diagnostic information, although intestinal gas and abdominal tenderness may limit its accuracy. To confirm the findings, magnetic resonance angiography (MRA) or CT angiography (CTA) can be used. In our case, the diagnosis was established using a color Doppler ultrasonography of the abdomen and was later confirmed by a low dose CT scan of the abdominal aorta. MRA in such cases have some disadvantages. At many health centers, the monitoring of patients with acute ruptures is more difficult in the MR suite than at the CT scanner. MRA angiographic images are also subject to degradation by multiple artifacts and the visualization of the distal vasculature is suboptimal and inferior to the one done by CTA. Due to fetal movements, a small quantity of fresh blood can be overlooked by MR. MRA is often not available on a 24-hours basis, and the time required for making a diagnosis can preclude the use of MRA in an unstable patient. For this reason, we used a low dose CTA protocol to confirm the diagnosis. Low dose scanning protocols in CT can obtain sufficient diagnostic information while reducing the risk of radiation. A particular focus is put on the outline of new concepts for dose management and optimization. We used new approaches based on tube current modulation. The birth was induced by an urgent Caesarean section followed by a resection of a pseudoaneurysm and a reconstruction of the aorta with an end-to-end vascular prosthesis. PMID:26898082

  17. Low dose scatter correction for digital chest tomosynthesis

    NASA Astrophysics Data System (ADS)

    Inscoe, Christina R.; Wu, Gongting; Shan, Jing; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping

    2015-03-01

    Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.

  18. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy.

  19. The Effects of ELDRS at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al

    2011-01-01

    We present results on the effects on ELDRS at dose rates of 10, 5, 1, and 0.5 mrad(Si)/s for a variety of radiation hardened and commercial devices. We observed low dose rate enhancement below 10 mrad(Si)/s in several different parts. The magnitudes of the dose rate effects vary. The TL750L, a commercial voltage regulator, showed dose rate dependence in the functional failures, with initial failures occurring after 10 krad(Si) for the parts irradiated at 0.5 mrad(Si)/s. The RH1021 showed an increase in low dose rate enhancement by 2x at 5 mrad(Si)/s relative to 8 mrad(Si)/s and high dose rate, and parametric failure after 100 krad(Si). Additionally the ELDRS-free devices, such as the LM158 and LM117, showed evidence of dose rate sensitivity in parametric degradations. Several other parts also displayed dose rate enhancement, with relatively lower degradations up to approx.15 to 20 krad(Si). The magnitudes of the dose rate enhancement will likely increase in significance at higher total dose levels.

  20. Porous hydroxyapatite tablets as carriers for low-dosed drugs.

    PubMed

    Cosijns, A; Vervaet, C; Luyten, J; Mullens, S; Siepmann, F; Van Hoorebeke, L; Masschaele, B; Cnudde, V; Remon, J P

    2007-09-01

    The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250 degrees C) revealed tablets with an acceptable friability (<1%). Using 50% (w/w) Avicel PH 200 as pore forming agent resulted in tablets combining the highest porosity (50%) and the highest median pore diameter (5 microm). Aqueous drug solutions (metoprolol tartrate, riboflavin sodium phosphate) were spiked on the tablet surface. The maximum volume of drug solution absorbed was limited (2x100 microl), revealing that these porous carriers were ideal for low dosed formulations. Drug release from the tablets was slow, independent of the drug. To accelerate drug release, tablets were manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80 microm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.

  1. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M. ); Panozzo, J.; Libertin, C.R. )

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following [gamma]-ray exposure in fibroblasts. Our past work had shown differences in the expression of [beta]-protein kinase C and c-fos genes, both being induced following [gamma]-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not [gamma]-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to [gamma] rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  2. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-06-01

    Studies were designed to identify genes induced following low-dose neutron but not following {gamma}-ray exposure in fibroblasts. Our past work had shown differences in the expression of {beta}-protein kinase C and c-fos genes, both being induced following {gamma}-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not {gamma}-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to {gamma} rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  3. Non linear processes modulated by low doses of radiation exposure

    NASA Astrophysics Data System (ADS)

    Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

    The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

  4. Effect of low dose rate radiation on cell growth kinetics.

    PubMed Central

    Gregg, E C; Yau, T M; Kim, S C

    1979-01-01

    Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization. PMID:262446

  5. A New Era of Low-Dose Radiation Epidemiology.

    PubMed

    Kitahara, Cari M; Linet, Martha S; Rajaraman, Preetha; Ntowe, Estelle; Berrington de González, Amy

    2015-09-01

    The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies. PMID:26231501

  6. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy. PMID:26609683

  7. Low-dose aripiprazole for refractory burning mouth syndrome.

    PubMed

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  8. Quantifying exploratory low dose compounds in humans with AMS

    PubMed Central

    Dueker, Stephen R.; Vuong, Le T.; Lohstroh, Peter N.; Giacomo, Jason A.; Vogel, John S.

    2010-01-01

    Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS 14C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research. PMID:21047543

  9. Optical fiber sensor for low dose gamma irradiation monitoring

    NASA Astrophysics Data System (ADS)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  10. Low-dose aripiprazole for refractory burning mouth syndrome

    PubMed Central

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  11. The spectrum of mutation produced by low dose radiation

    SciTech Connect

    Morley,Alexander,A; Turner, David,R

    2004-10-31

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  12. Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions

    SciTech Connect

    Davison, R.; Kaplan, K.; Bines, A.; Spies, S.; Reed, M.T.; Lesch, M.

    1986-12-01

    Thallium 201 (/sup 201/Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial /sup 201/Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

  13. Low-dose radiation: a cause of breast cancer

    SciTech Connect

    Land, C.E.

    1980-08-15

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.

  14. Radiobiological evaluation of low dose-rate prostate brachytherapy implants

    NASA Astrophysics Data System (ADS)

    Knaup, Courtney James

    Low dose-rate brachytherapy is a radiation therapy treatment for men with prostate cancer. While this treatment is common, the use of isotopes with varying dosimetric characteristics means that the prescription level and normal organ tolerances vary. Additionally, factors such as prostate edema, seed loss and seed migration may alter the dose distribution within the prostate. The goal of this work is to develop a radiobiological response tool based on spatial dose information which may be used to aid in treatment planning, post-implant evaluation and determination of the effects of prostate edema and seed migration. Aim 1: Evaluation of post-implant prostate edema and its dosimetric and biological effects. Aim 2: Incorporation of biological response to simplify post-implant evaluation. Aim 3: Incorporation of biological response to simplify treatment plan comparison. Aim 4: Radiobiologically based comparison of single and dual-isotope implants. Aim 5: Determine the dosimetric and radiobiological effects of seed disappearance and migration.

  15. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  16. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    SciTech Connect

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  17. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGES

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; et al

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initiallymore » improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

  18. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    PubMed Central

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy. PMID:25337914

  19. Low-dose metronomic chemotherapy: a systematic literature analysis.

    PubMed

    Lien, K; Georgsdottir, S; Sivanathan, L; Chan, K; Emmenegger, U

    2013-11-01

    Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is an emerging alternative to conventional chemotherapy. While promising tumour control rates and excellent safety profiles have been observed, there are no definitive phase III trial results. Furthermore, the selection of patients, drug dosages and dosing intervals is empirical. To systematically review the current state of knowledge regarding LDM chemotherapy, we searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for fully published LDM chemotherapy trials. We calculated the relative dose-intensity (RDI, mg/m(2)/week) of each LDM regimen as compared to conventional maximum tolerated dose (MTD) dosages and the 'dosing-density' (DD, % of days with chemotherapy administration per cycle). Meta-regression was performed to examine factors associated with disease control rate (DCR; complete response (CR)+partial response (PR)+stable disease (SD)). Eighty studies involving mainly pretreated patients with advanced/metastatic breast (26.25%) and prostate (11.25%) cancers were retrieved. The most commonly used drug was cyclophosphamide (43%). LDM chemotherapy was frequently combined with other therapies (64.5%). Response rate (RR) and progression-free survival (PFS) were the most frequent primary end-points (24% and 19%). Mean RR was 26.03% (95% confidence interval (CI): 21.4-30.7), median PFS was 4.6months (interquartile range (IQR): 2.9-7.0) and mean DCR was 56.3% (95% CI: 50.9-61.6). RDI, DD and metronomic drug used were not associated with DCR. Grade 3/4 adverse events were rare (anaemia 7.78%, fatigue 13.4%). Thus, LDM therapy appears to be clinically beneficial and safe in a broad range of tumors. However, meta-regression analysis did not identify predictive factors of response.

  20. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    SciTech Connect

    Kleiman, Norman Jay

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  1. Migration of a strand of four seeds in low-dose-rate brachytherapy

    PubMed Central

    Dedic-Hagan, Jasmina; Teh, Amy Y M; Liang, Eisen; Collett, Nicholas; Woo, Henry H

    2014-01-01

    We report a case of stranded-seed migration (one strand of four seeds), via the prostatic venous plexus to the internal pudendal vein, in low-dose-rate (LDR) prostate brachytherapy. A 70-year-old man with low-risk prostate adenocarcinoma underwent transperineal permanent seed implantation. A total of 93 iodine-125 seeds were implanted (91 stranded seeds and 2 loose seeds). Immediate postimplantation fluoroscopic image and day 1 postimplantation CT scan indicated all implanted seeds to be within the vicinity of the prostate as planned. Day 30 pelvic X-ray and CT scan revealed migration of a strand of four seeds to the right pelvis (adjacent to ischial spine). At 2 years postimplantation, the patient continues to have good disease control with prostate specific antigen level of 0.69 μg/L, and asymptomatic. To the best of our knowledge, this is the first report of migration of an entire strand of seeds following LDR prostate brachytherapy. PMID:24879735

  2. Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.

    PubMed

    Hasan, Naveed; Kumar, Rohit; Kavuru, Mani S

    2014-10-01

    Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use. Furthermore, a lung nodule on CT scan requires a nuanced and individualized approach towards management. In this regard, advances in high through-put technology (molecular diagnostics, multi-gene chips, proteomics, and bronchoscopic techniques) have led to discovery of lung cancer biomarkers that have shown potential to complement the current screening standards. Early detection of lung cancer can be achieved by analysis of biomarkers from tissue samples within the respiratory tract such as sputum, saliva, nasal/bronchial airway epithelial cells and exhaled breath condensate or through peripheral biofluids such as blood, serum and urine. Autofluorescence bronchoscopy has been employed in research setting to identify pre-invasive lesions not identified on CT scan. Although these modalities are not yet commercially available in clinic setting, they will be available in the near future and clinicians who care for patients with lung cancer should be aware. In this review, we present up-to-date state of biomarker development, discuss their clinical relevance and predict their future role in lung cancer management.

  3. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    SciTech Connect

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  4. Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain.

    PubMed

    Mao, Xiao Wen; Nishiyama, Nina C; Pecaut, Michael J; Campbell-Beachler, Mary; Gifford, Peter; Haynes, Kristine E; Becronis, Caroline; Gridley, Daila S

    2016-06-01

    Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence

  5. Evaluation of low-dose limits in 3D-2D rigid registration for surgical guidance

    NASA Astrophysics Data System (ADS)

    Uneri, A.; Wang, A. S.; Otake, Y.; Kleinszig, G.; Vogt, S.; Khanna, A. J.; Gallia, G. L.; Gokaslan, Z. L.; Siewerdsen, J. H.

    2014-09-01

    An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image + guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image + guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

  6. Responses to Low Doses of Ionizing Radiation in Biological Systems

    PubMed Central

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems. To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses. The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed

  7. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals. PMID:24772825

  8. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

    PubMed Central

    Seed, Thomas M.; Inal, Cynthia E.

    2014-01-01

    Purpose Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie? Material and methods C3H/HEN mice were administered varying doses of amifostine (25–100 mg/kg) 30 min prior to cobalt-60 irradiation and euthanized between 4–14 days for blood and bone marrow collection and analyses. Results Under steady-state, amifostine had little effect on bipotential and multi-potential marrow progenitors but marginally suppressed a more primitive, lineage negative progenitor subpopulation. In irradiated animals, prophylactic drug doses greater than 50 mg/kg resulted in significant regeneration of bipotential progenitors, moderate regeneration of multipotential progenitors, but no significant and consistent regeneration of more primitive progenitors. The low amifostine dose (25 mg/kg) failed to elicit consistent and positive, radioprotective actions on any of the progenitor subtypes. Conclusions Radioprotective doses for amifostine appear to lie between 25 and 50 mg/kg. Mature, lineage-restricted progenitors appear to be more responsive to the protective effects of low doses of amifostine than the more primitive, multipotential progenitors. PMID:24597748

  9. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    NASA Astrophysics Data System (ADS)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  10. Dosimetric Study of a Low-Dose-Rate Brachytherapy Source

    NASA Astrophysics Data System (ADS)

    Rodríguez-Villafuerte, M.; Arzamendi, S.; Díaz-Perches, R.

    Carcinoma of the cervix is the most common malignancy - in terms of both incidence and mortality - in Mexican women. Low dose rate (LDR) intracavitary brachytherapy is normally prescribed for the treatment of this disease to the vast majority of patients attending public hospitals in our country. However, most treatment planning systems being used in these hospitals still rely on Sievert integral dose calculations. Moreover, experimental verification of dose distributions are hardly ever done. In this work we present a dosimetric characterisation of the Amersham CDCS-J 137Cs source, an LDR brachytherapy source commonly used in Mexican hospitals. To this end a Monte Carlo simulation was developed, that includes a realistic description of the internal structure of the source embedded in a scattering medium. The Monte Carlo results were compared to experimental measurements of dose distributions. A lucite phantom with the same geometric characteristics as the one used in the simulation was built. Dose measurements were performed using thermoluminescent dosimeters together with commercial RadioChromic dye film. A comparison between our Monte Carlo simulation, the experimental data, and results reported in the literature is presented.

  11. Sensitivity to low-dose radiation in radiosensitive wasted mice

    SciTech Connect

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-11-12

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells.

  12. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  13. Risk of cancer subsequent to low-dose radiation.

    PubMed

    Warren, S

    1980-10-01

    Prominent among media items related to the Three Mile Island episode were prophecies of future cancers. The credibility of some of these estimates are discussed. The average person has been exposed by the age of 50 to 2.5 rad (0.025 Gy) from natural background. We define low doses as under 25 rad (0.25 Gy). The most heavily exposed members of the general population during the Three Mile Island event received 83 mrad (0.83 mGy). Those exposed to 2500 mrad (25 mGy) would show no pathologically recognizable effects of radiation though there is evidence that chromosomal damage may occur with doses about 1 rad (0.01 Gy). An official stated among the consequences of the Three Mile Island accident that two additional cancer deaths would result. No epidemiologist could detect such an increase in the population at risk. It has been generally agreed that the linear hypothesis is useful for determining protection standards, not prognosis. Objective criteria for pathologic diagnosis of cause-effect relations are presented. PMID:7430985

  14. Information content of low-dose radiographs: Part 2

    SciTech Connect

    Morris, R.A.

    1997-10-01

    The previous paper described the concept of using the net number of information bits transmitted in a radiographic image as a measure of the contrast parameter of image quality. The concept is particularly useful when the image contrast is limited by the statistics of the photon fluence incident on the detector (low doses). The Wolfram Research Mathematica program (described in Ref. 1) that was used to simulate a noisy image of an object with two thicknesses and to calculate the resulting IC (information content). The only noise source in the simulation was fluctuations in the photon fluence incident on the detector. The results from the simulation were compared to data obtained from actual radiographs of a copper step wedge radiographed with 10 and 50 pulses from a 150-p, V x-ray machine. Good agreement between the simulation and experiment was obtained when the photon fluence was considered a free, adjustable parameter. This report extends the simulation described in Ref. 1 and shows how IC varies as the following radiographic parameters change: object thickness; object Z number; x-ray energy; and incident x-ray fluence.

  15. Functional modulation on macrophage by low dose naltrexone (LDN).

    PubMed

    Yi, Zhe; Guo, Shengnan; Hu, Xu; Wang, Xiaonan; Zhang, Xiaoqing; Griffin, Noreen; Shan, Fengping

    2016-10-01

    Previously it was confirmed that naltrexone, a non-peptide δ-opioid receptor selective antagonist is mainly used for alcoholic dependence and opioid addiction treatment. However, there is increasing data on immune regulation of low dose naltrexone (LDN). The aim of this work was to explore the effect of LDN on the phenotype and function of macrophage. The changes of macrophage after treatment with LDN were examined using flow cytometry (FCM); FITC-dextran phagocytosis and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances function of macrophage as confirmed by up-regulating MHC II molecule and CD64 on macrophage while down-regulating CD206 expression. Furthermore the productions of TNF-α, IL-6, IL-1β, increased significantly. Macrophages in LDN treated group performed the enhanced phagocytosis. Therefore it is concluded that LDN could promote function of macrophage and this work has provided concrete data of impact on immune system by LDN. Especially the data would support interaction between CD4+T cell and macrophage in AIDS treatment with LDN in Africa (LDN has already been approved in Nigeria for the use in AIDS treatment). PMID:27561742

  16. Low-dose diclofenac, naproxen, and ibuprofen cohort study.

    PubMed

    Pérez-Gutthann, S; García-Rodríguez, L A; Duque-Oliart, A; Varas-Lorenzo, C

    1999-07-01

    The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (< or = 75 mg), 46,919 using naproxen (< or = 750 mg), and 54,830 using ibuprofen (< or = 1200 mg). Age, gender, and comorbidity were similar in the three cohorts. Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5-4.6), 2.3 (1.2-4.2), and 0.4 (0.04-1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.

  17. Role of heme Oxygenase-1 in low dose Radioadaptive response

    PubMed Central

    Bao, Lingzhi; Ma, Jie; Chen, Guodong; Hou, Jue; Hei, Tom K.; Yu, K.N.; Han, Wei

    2016-01-01

    Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1–10 cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5 cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells. PMID:26966892

  18. Automated aortic calcium scoring on low-dose chest computed tomography

    SciTech Connect

    Isgum, Ivana; Rutten, Annemarieke; Prokop, Mathias; Staring, Marius; Klein, Stefan; Pluim, Josien P. W.; Viergever, Max A.; Ginneken, Bram van

    2010-02-15

    Purpose: Thoracic computed tomography (CT) scans provide information about cardiovascular risk status. These scans are non-ECG synchronized, thus precise quantification of coronary calcifications is difficult. Aortic calcium scoring is less sensitive to cardiac motion, so it is an alternative to coronary calcium scoring as an indicator of cardiovascular risk. The authors developed and evaluated a computer-aided system for automatic detection and quantification of aortic calcifications in low-dose noncontrast-enhanced chest CT. Methods: The system was trained and tested on scans from participants of a lung cancer screening trial. A total of 433 low-dose, non-ECG-synchronized, noncontrast-enhanced 16 detector row examinations of the chest was randomly divided into 340 training and 93 test data sets. A first observer manually identified aortic calcifications on training and test scans. A second observer did the same on the test scans only. First, a multiatlas-based segmentation method was developed to delineate the aorta. Segmented volume was thresholded and potential calcifications (candidate objects) were extracted by three-dimensional connected component labeling. Due to image resolution and noise, in rare cases extracted candidate objects were connected to the spine. They were separated into a part outside and parts inside the aorta, and only the latter was further analyzed. All candidate objects were represented by 63 features describing their size, position, and texture. Subsequently, a two-stage classification with a selection of features and k-nearest neighbor classifiers was performed. Based on the detected aortic calcifications, total calcium volume score was determined for each subject. Results: The computer system correctly detected, on the average, 945 mm{sup 3} out of 965 mm{sup 3} (97.9%) calcified plaque volume in the aorta with an average of 64 mm{sup 3} of false positive volume per scan. Spearman rank correlation coefficient was {rho}=0.960 between

  19. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully.

  20. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID:26808877

  1. Evaluation of a low-dose neonatal chest radiographic system.

    PubMed

    Burton, E M; Kirks, D R; Strife, J L; Henry, G C; Kereiakes, J G

    1988-11-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

  2. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. PMID:27302731

  3. Evaluation of a low-dose neonatal chest radiographic system

    SciTech Connect

    Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

    1988-11-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad (0.009 vs 0.029 mGy)) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad (0.009 vs 0.037 mGy)). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

  4. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose.

  5. Lung cancer risk at low doses of alpha particles.

    PubMed

    Hofmann, W; Katz, R; Zhang, C X

    1986-10-01

    A survey of inhabitant exposures arising from the inhalation of 222Rn and 220Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the "high background" and the "control" area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 222Rn and 220Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli.

  6. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  7. Effect of low-dose gaseous ozone on pathogenic bacteria

    PubMed Central

    2012-01-01

    Background Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes. Methods A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O3/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used. Results The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups. Conclusion A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents. PMID:23249441

  8. Low dose of propranolol does not affect rat osteotomy healing and callus strength

    PubMed Central

    Smitham, Peter; Crossfield, Lawrence; Hughes, Gillian; Goodship, Allen; Blunn, Gordon; Chenu, Chantal

    2014-01-01

    Experimental studies suggest that the β-blocker propranolol stimulates bone formation but little work has investigated its effect on fracture healing. In this study, we examined if a low dose of propranolol, previously shown to be preventive against bone loss in rats, improves bone repair. Female Wistar rats were injected with saline or propranolol (0.1 mg/kg/day) (n = 20/group), 5 days a week for 8 weeks. Three weeks after the beginning of treatment, all rats underwent a mid-diaphyseal transverse osteotomy in the left femur. Radiographic analysis of ostetomy healing was performed 2 and 5 weeks after osteotomy. Rats were sacrificed at 5 weeks and femora collected for measurements of fracture strength by torsional testing, callus volume, and mineral content by micro-CT analysis and histology of fracture callus. Eighty nine percent of osteotomies achieved apparent radiological union by 5 weeks in both groups. Propranolol treatment did not significantly alter the torsional strength of the fractured femur compared with controls. The volume and mineralization of fracture callus at 5 weeks were not significantly different in both groups. Histology showed that endochondral ossification was not affected by propranolol. Altogether, our results demonstrate that propranolol using the regimen described does not significantly improve or inhibit rat osteotomy healing and mechanical strength. PMID:24710688

  9. The MAGIC-5 CAD for nodule detection in low dose and thin slice lung CTs

    NASA Astrophysics Data System (ADS)

    Cerello, Piergiorgio; MAGIC-5 Collaboration

    2010-11-01

    Lung cancer is the leading cause of cancer-related mortality in developed countries. Only 10-15% of all men and women diagnosed with lung cancer live 5 years after the diagnosis. However, the 5-year survival rate for patients diagnosed in the early asymptomatic stage of the disease can reach 70%. Early-stage lung cancers can be diagnosed by detecting non-calcified small pulmonary nodules with computed tomography (CT). Computer-aided detection (CAD) could support radiologists in the analysis of the large amount of noisy images generated in screening programs, where low-dose and thin-slice settings are used. The MAGIC-5 project, funded by the Istituto Nazionale di Fisica Nucleare (INFN, Italy) and Ministero dell'Università e della Ricerca (MUR, Italy), developed a multi-method approach based on three CAD algorithms to be used in parallel with a merging of their results: the Channeler Ant Model (CAM), based on Virtual Ant Colonies, the Dot-Enhancement/Pleura Surface Normals/VBNA (DE-PSN-VBNA), and the Region Growing Volume Plateau (RGVP). Preliminary results show quite good performances, to be improved with the refining of the single algorithm and the added value of the results merging.

  10. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  11. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    SciTech Connect

    Al-Qaisieh, Bashar; Mason, Josh; Bownes, Peter; Henry, Ann; Dickinson, Louise; Ahmed, Hashim U.; Emberton, Mark; Langley, Stephen

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  12. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    SciTech Connect

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  13. The effects of repeated low-dose sarin exposure

    SciTech Connect

    Shih, T.-M. . E-mail: tsungming.a.shih@us.army.mil; Hulet, S.W.; McDonough, J.H.

    2006-09-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD{sub 5} dose of sarin (42 {mu}g/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD{sub 5} of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD{sub 5} of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD{sub 5} sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD{sub 5} sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD{sub 5} sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD{sub 5} sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0

  14. Long-term prognosis of patients with lung cancer detected on low-dose chest computed tomography screening.

    PubMed

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Kusano, Suzushi; Chonan, Tatsuya; Fukai, Shimao; Endo, Katsuyuki

    2012-02-01

    The effectiveness of lung cancer screening using low-dose chest computed tomography (CT) remains elusive. The present study examined the prognosis of patients with lung cancer detected on CT screening in Japanese men and women. Subjects were 210 patients with primary lung cancer identified on CT screening at two medical facilities in Hitachi, Japan, where a total of 61,914 CT screenings were performed among 25,385 screenees between 1998 and 2006. Prognostic status of these patients was sought by examining medical records at local hospitals, supplemented by vital status information from local government. The 5-year survival rate was estimated according to the characteristics of patients and lung nodule. A total of 203 (97%) patients underwent surgery. During a 5.7-year mean follow-up period, 19 patients died from lung cancer and 6 died from other causes. The estimated 5-year survival rate for all patients and for those on stage IA was 90% and 97%, respectively. Besides cancer stage, smoking and nodule appearance were independent predictors of a poor survival; multivariable-adjusted hazard ratio (95% confidence interval) was 4.7 (1.3, 16.5) for current and past smokers versus nonsmokers and 4.6 (1.6, 13.9) for solid nodule versus others. Even patients with solid shadow had a 5-year survival of 82% if the lesion was 20mm or less in size. Results suggest that lung cancers detected on CT screening are mostly curative. The impact of CT screening on mortality at community level needs to be clarified by monitoring lung cancer deaths.

  15. Coronary artery calcium score on low-dose computed tomography for lung cancer screening

    PubMed Central

    Arcadi, Teresa; Maffei, Erica; Sverzellati, Nicola; Mantini, Cesare; Guaricci, Andrea I; Tedeschi, Carlo; Martini, Chiara; La Grutta, Ludovico; Cademartiri, Filippo

    2014-01-01

    AIM: To evaluate the feasibility of coronary artery calcium score (CACS) on low-dose non-gated chest CT (ngCCT). METHODS: Sixty consecutive individuals (30 males; 73 ± 7 years) scheduled for risk stratification by means of unenhanced ECG-triggered cardiac computed tomography (gCCT) underwent additional unenhanced ngCCT. All CT scans were performed on a 64-slice CT scanner (Somatom Sensation 64 Cardiac, Siemens, Germany). CACS was calculated using conventional methods/scores (Volume, Mass, Agatston) as previously described in literature. The CACS value obtained were compared. The Mayo Clinic classification was used to stratify cardiovascular risk based on Agatston CACS. Differences and correlations between the two methods were compared. A P-value < 0.05 was considered significant. RESULTS: Mean CACS values were significantly higher for gCCT as compared to ngCCT (Volume: 418 ± 747 vs 332 ± 597; Mass: 89 ± 151 vs 78 ± 141; Agatston: 481 ± 854 vs 428 ± 776; P < 0.05). The correlation between the two values was always very high (Volume: r = 0.95; Mass: r = 0.97; Agatston: r = 0.98). Of the 6 patients with 0 Agatston score on gCCT, 2 (33%) showed an Agatston score > 0 in the ngCCT. Of the 3 patients with 1-10 Agatston score on gCCT, 1 (33%) showed an Agatston score of 0 in the ngCCT. Overall, 23 (38%) patients were reclassified in a different cardiovascular risk category, mostly (18/23; 78%) shifting to a lower risk in the ngCCT. The estimated radiation dose was significantly higher for gCCT (DLP 115.8 ± 50.7 vs 83.8 ± 16.3; Effective dose 1.6 ± 0.7 mSv vs 1.2 ± 0.2 mSv; P < 0.01). CONCLUSION: CACS assessment is feasible on ngCCT; the variability of CACS values and the associated re-stratification of patients in cardiovascular risk groups should be taken into account. PMID:24976939

  16. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  17. Low doses of glyphosate change the response of soybean to later glyphosate exposures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The stimulatory effect of low doses of toxic substances is known as hormesis. Many herbicides that cause severe injury to plants at recommended rates, promote growth or have other stimulatory effects at very low doses. The objective of this study was to evaluate glyphosate-induced hormesis in soyb...

  18. Effects of Low Dose FGF-2 and BMP-2 on Healing of Calvarial Defects in Old Mice

    PubMed Central

    Charles, Lyndon F.; Woodman, Jessica L.; Ueno, Daisuke; Gronowicz, Gloria; Hurley, Marja M.; Kuhn, Liisa T.

    2015-01-01

    There is an age-associated reduction in the bone healing activity of bone morphogenetic protein -2 (BMP-2) that is currently addressed by administering higher doses of BMP-2 in elderly patients. The unwanted medical complications from high dose BMP-2 motivated this investigation to determine whether the addition of a low dose of fibroblast growth factor 2 (FGF-2) could enhance the ability of a lower dose of BMP-2 to heal calvarial bone defects in old mice (18-20 months old). FGF-2 (5 ng) and BMP-2 (2 μg) were administered by a controlled release two-phase biomaterial scaffold placed into the bone defect. FGF-2 released more rapidly and completely in vitro than BMP-2 (40% vs 2%). In vivo, both BMP-2 and FGF-2+BMP-2 groups formed more new bone in calvarial defects than scaffold alone (p <0.001) or FGF-2 only groups (p < 0.01). The overall total volume of new bone was not statistically increased by the addition of FGF-2 to BMP-2 as measured by microCT, but the pattern of bone deposition was different. In old mice, but not young, there was enhanced bony fill in the central bone defect area when the BMP-2 was supplemented with FGF-2. Histological analysis of the center of the defect revealed an increased bone volume (%BV/TV (p = 0.004)) from the addition of FGF-2. These studies suggest that combining a low dose of FGF-2 with a low dose of BMP-2 has the potential to increase bone healing in old mice relative to BMP-2 alone. PMID:25681640

  19. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    PubMed Central

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  20. Low-dose megavoltage cone-beam computed tomography for lung tumors using a high-efficiency image receptor

    SciTech Connect

    Sillanpaa, Jussi; Chang Jenghwa; Mageras, Gikas; Yorke, Ellen; Arruda, Fernando De; Rosenzweig, Kenneth E.; Munro, Peter; Seppi, Edward; Pavkovich, John; Amols, Howard

    2006-09-15

    We report on the capabilities of a low-dose megavoltage cone-beam computed tomography (MV CBCT) system. The high-efficiency image receptor consists of a photodiode array coupled to a scintillator composed of individual CsI crystals. The CBCT system uses the 6 MV beam from a linear accelerator. A synchronization circuit allows us to limit the exposure to one beam pulse [0.028 monitor units (MU)] per projection image. 150-500 images (4.2-13.9 MU total) are collected during a one-minute scan and reconstructed using a filtered backprojection algorithm. Anthropomorphic and contrast phantoms are imaged and the contrast-to-noise ratio of the reconstruction is studied as a function of the number of projections and the error in the projection angles. The detector dose response is linear (R{sup 2} value 0.9989). A 2% electron density difference is discernible using 460 projection images and a total exposure of 13 MU (corresponding to a maximum absorbed dose of about 12 cGy in a patient). We present first patient images acquired with this system. Tumors in lung are clearly visible and skeletal anatomy is observed in sufficient detail to allow reproducible registration with the planning kV CT images. The MV CBCT system is shown to be capable of obtaining good quality three-dimensional reconstructions at relatively low dose and to be clinically usable for improving the accuracy of radiotherapy patient positioning.

  1. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    SciTech Connect

    Morgan, William F.; von Borstel, Robert C.; Brenner, David; Redpath, J. Leslie; Erickson, Barbra E.; Brooks, Antone L.

    2009-11-12

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects.

  2. Low Doses of Radiation are Protective In Vitro and In Vivo: Evolutionary Origins

    PubMed Central

    Mitchel, R.E.J.

    2006-01-01

    Research reports using cells from bacteria, yeast, alga, nematodes, fish, plants, insects, amphibians, birds and mammals, including wild deer, rodents or humans show non-linear radio-adaptive processes in response to low doses of low LET radiation. Low doses increased cellular DNA double-strand break repair capacity, reduced the risk of cell death, reduced radiation or chemically-induced chromosomal aberrations and mutations, and reduced spontaneous or radiation-induced malignant transformation in vitro. In animals, a single low, whole body dose of low LET radiation, increased cancer latency and restored a portion of the life that would have been lost due to either spontaneous or radiation-induced cancer in the absence of the low dose. In genetically normal fetal mice, a prior low dose protected against radiation-induced birth defects. In genetically normal adultmale mice, a low dose prior to a high dose protected the offspring of the mice from heritable mutations produced by the large dose. The results show that low doses of low-LET radiation induce protective effects and that these induced responses have been tightly conserved throughout evolution, suggesting that they are basic responses critical to life. The results also argue strongly that the assumption of a linear increase in risk with increasing dose in humans is unlikely to be correct, and that low doses actually reduce risk. PMID:18648638

  3. Local application of low-dose insulin in improving wound healing after deep burn surgery

    PubMed Central

    Wang, Chejiang; Wang, Jiazhe; Feng, Jianke

    2016-01-01

    The clinical effects of local application of low-dose insulin in improving wound healing after deep burn self-skin transplantation surgery were examined. Fifty-eight patients with deep burns were selected and randomly divided into 3 groups. In the blank control group, normal saline was injected to the subcutaneous tissue of wounds; in large dose insulin group, 1.0 µ long-term suspended zinc insulin was locally injected; and in the low-dose insulin group, 0.1 µ long-term suspended zinc insulin was locally injected. The healing effects were compared. After 7 and 14 days of treatments, wound surface area in the low-dose group was significantly smaller than in the other groups, and differences were statistically significant (P<0.05); wound healing duration and infection rate for patients in the low-dose group were significantly lower, class A healing rate was significantly improved, and the differences were statistically significant (P<0.05). Insulin resistance index (HOMA-IR) in the low-dose group was significantly lower, insulin secretion index (HOMA-β) and the insulin sensitivity index (HOMA-ISI) significantly increased. The expression levels of vascular endothelial growth factor and tumor necrosis factor-α in local tissue for the low-dose group were significantly higher than those in the other two groups. Differences were statistically significant (P<0.05). In conclusion, local application of low-dose insulin can effectively improve wound healing after deep burn surgeries.

  4. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    PubMed

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-01-01

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen. PMID:26515758

  5. Cost-effectiveness analysis of lung cancer screening with low-dose computerised tomography of the chest in Poland

    PubMed Central

    Szczęsny, Tomasz J.; Krysiński, Jerzy; Buciński, Adam; Kowalewski, Janusz; Pawłowicz, Zbigniew

    2015-01-01

    Aim of the study To determine the cost-effectiveness of lung cancer (LC) screening with low-dose computerised tomography of the chest, as compared to an approach without screening, reimbursed today by the National Health Fund (NHF) in Poland. Material and methods In order to analyse the current costs of diagnostic and therapeutic procedures of a model LC patient treated today, a model group consisting of 199 consecutive patients diagnosed and treated in the Oncology Centre in Bydgoszcz, Poland from January 2007 to April 2010 was used. The number and type of performed procedures in this group was obtained from the Polish Register of Neoplasms and the NHF. Only direct medical costs were analysed. To calculate the total costs of screening, diagnostics, and treatment of the hypothetical LC patient who would have cancer diagnosed with screening CT, data from the literature and costs calculated for the model group were used. Prices of procedures were obtained from the price list of the NHF on 30 April 2010 and did not change from that time until June 2014. One-way sensitivity analysis was performed. Results The average cost per LC patient, diagnosed and treated without screening, is 5567.50 EUR, and median LC-specific survival is one year. In the hypothetical LC patient with cancer diagnosed by screening, the average cost is 13689.35 EUR per LC patient, with a median LC-specific survival of at least seven years. A calculated incremental cost-effectiveness ratio (ICER) is 1353.64 EUR/year of life gained. Conclusions Lung cancer screening with low-dose CT would be highly cost-effective in Poland. PMID:26843847

  6. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    SciTech Connect

    Chung, Eugene; Corbett, James R.; Moran, Jean M.; Griffith, Kent A.; Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L.; Ficaro, Edward C.; Pierce, Lori J.

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  7. Diagnostic Performance on Low Dose Computed Tomography For Acute Appendicitis Among Attending and Resident Radiologists

    PubMed Central

    Chang, Chih-Chen; Wong, Yon-Cheong; Wu, Cheng-Hsien; Chen, Huan-Wu; Wang, Li-Jen; Lee, Yu-Hsien; Wu, Patricia Wanping; Irama, Wiwan; Chen, Wei Yuan; Chang, Chee-Jen

    2016-01-01

    Background Low-dose computed tomography (LDCT) techniques can reduce exposure to radiation. Several previous studies have shown that radiation dose reduction in LDCT does not decrease the diagnostic performance for appendicitis among attending radiologists. But, the LDCT diagnostic performance for acute appendicitis in radiology residents with variable training levels has not been well discussed. Objectives To compare inter-observer and intra-observer differences of diagnostic performance on non-enhanced LDCT (NE-LDCT) and contrast-enhanced standard dose CT (CE-SDCT) for acute appendicitis among attending and resident radiologists. Patients and Methods This retrospective study included 101 patients with suspected acute appendicitis who underwent NE-LDCT and CE-SDCT. The CT examinations were interpreted and recorded on a five-point scale independently by three attending radiologists and three residents with 4, 1 and 1 years of training. Diagnostic performance for acute appendicitis of all readers on both examinations was represented by area under receiver operating characteristic (ROC) curves. Inter-observer and intra-observer AUC values were compared using Jackknife FROC software on both modalities. The diagnostic accuracy of each reader on NE-LDCT was compared with body mass index (BMI) subgroups and noise using independent T test. Results Diagnostic performances for acute appendicitis were not statistically different for attending radiologists at both examinations. Better performance was noted on the CE-SDCT with a borderline significant difference (P = 0.05) for senior radiology resident. No statistical difference of AUC values was observed between attending radiologists and fourth year resident on both examinations. Statistically significant differences of AUC values were observed between attending radiologists and first year residents (P = 0.001 ~ 0.018) on NE-LDCT. Diagnostic accuracies of acute appendicitis on NE-LDCT for each reader were not significantly

  8. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  9. Changes in thyroid status of rats after prolonged exposure to low dose dichlorodiphenyltrichloroethane.

    PubMed

    Yaglova, N V; Yaglov, V V

    2014-04-01

    The effect of low dose dichlorodiphenyltrichloroethane (DDT), omnipresent ecotoxicant and endocrine disruptor, on the functioning of the endocrine system is an urgent problem. We studied the effect of low dose DDT on thyroid status in rats. Rats receiving DDT in a dose of 1.890±0.086 μg/kg for 6 weeks showed increased concentrations of thyroid hormones, particularly triiodothyronine, and reduced level of thyrotropin. Longer exposure reduced the production of thyroid hormones. The dynamics of thyroid status parameters during DDT treatment in a low dose was similar to changes observed during the development of hypothyroidism induced by iodine deficiency. PMID:24824690

  10. Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

    NASA Technical Reports Server (NTRS)

    Johnston, A.; Barnes, C.

    1995-01-01

    Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

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

    SciTech Connect

    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 scanned 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.

  12. Is there an advantage in performing a combined examination: diuretic renal scintigraphy and low dose computed tomography compared to the separate use of these methods in urolithiasis.

    PubMed

    Hadzhiyska, Valeriya; Kostadinova, Irena; Demirev, Anastas

    2015-01-01

    Ultrasonography (US), radiography of the kidneys, ureters and bladder (RKUB), intravenous urography (IVU) and especially non-enchanced CT are well established diagnostic modalities in screening patients with urolithiasis, while not always fully diagnostic especially when obstructive uropathy or calculous pyelonephritis are present . Diuretic renal scintigraphy (DRS) can determine obstruction, may differentiate between complete or partial, acute or chronic obstruction, but can not specify the cause and often the location of obstruction. The imaging protocol, including DRS with technetium-99m-mercaptylacetyltriglycine ((99m)Tc-MAG3) and single photon emission tomography/computed tomography (SPET/CT) of the kidneys, ureters, and urinary bladder allows for both functional and morphological information, visualization of renal stones and possible renal complications. The main advantages and limitations of this combined examination are discussed and the test is compared to the separate use of DRS and low dose of CT, in urolithiasis.

  13. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    PubMed Central

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  14. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Cancer.gov

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

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

    PubMed

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses. PMID:27218294

  16. [The advance of model of action in low-dose chronic benzene exposure induced hematotoxicity].

    PubMed

    Gao, Chen; Zhang, Zhengbao; Chen, Liping; Chen, Wen

    2015-09-01

    Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.

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

    PubMed

    Madas, Balázs G

    2016-07-01

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

  18. Pulsed low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis

    PubMed Central

    Cline-Smith, Anna; Gibbs, Jesse; Shashkova, Elena; Buchwald, Zachary S.

    2016-01-01

    A number of studies in model animal systems and in the clinic have established that RANKL promotes bone resorption. Paradoxically, we found that pulsing ovariectomized mice with low-dose RANKL suppressed bone resorption, decreased the levels of proinflammatory effector T cells and led to increased bone mass. This effect of RANKL is mediated through the induction of FoxP3+CD25+ regulatory CD8+ T cells (TcREG) by osteoclasts. Here, we show that pulses of low-dose RANKL are needed to induce TcREG, as continuous infusion of identical doses of RANKL by pump did not induce TcREG. We also show that low-dose RANKL can induce TcREG at 2, 3, 6, and 10 weeks after ovariectomy. Our results show that low-dose RANKL treatment in ovariectomized mice is optimal at once-per-month doses to maintain the bone mass. Finally, we found that treatment of ovariectomized mice with the Cathepsin K inhibitor odanacatib also blocked TcREG induction by low-dose RANKL. We interpret this result to indicate that antigens presented to CD8+ T cells by osteoclasts are derived from the bone protein matrix because Cathepsin K degrades collagen in the bone. Taken together, our studies provide a basis for using low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis. PMID:27570837

  19. Comparison of the Effects of Low-Dose Midazolam, Magnesium Sulfate, Remifentanil and Low-Dose Etomidate on Prevention of Etomidate-Induced Myoclonus in Orthopedic Surgeries

    PubMed Central

    Sedighinejad, Abbas; Naderi Nabi, Bahram; Haghighi, Mohammad; Biazar, Gelareh; Imantalab, Vali; Rimaz, Siamak; Zaridoost, Zahra

    2016-01-01

    Background Etomidate is a potent hypnotic agent with several desirable advantages such as providing a stable cardiovascular profile with minimal respiratory adverse effects and better hemodynamic stability compared with other induction agents. This drug is associated, however, with myoclonic movements which is characterized by a sudden, brief muscle contractions as a disturbing side-effect. Objectives The present study was designed to compare the effectiveness of low- dose midazolam, magnesium sulfate, remifentanil and low-dose etomidate to suppress etomidate-induced myoclonus in orthopedic surgery. Patients and Methods A double-blind clinical trial study was conducted in an academic hospital from September 2014 to August 2015. Two hundred and eighty-four eligible patients, American society of anesthesiologists class I - II, scheduled for elective orthopedic surgery were randomly allocated into four equal groups (n = 71). They received premedication with intravenous low-dose midazolam 0.015 mg/kg, magnesium sulfate 30 mg/kg, remifentanil 1 μg/kg and low-dose etomidate 0.03 mg/kg two minutes before induction of anesthesia with 0.3 mg/kg intravenous etomidate. Then the incidence and intensity of myoclonus were evaluated on a scale of 0 - 3; 0 = no myoclonus; 1 = mild (movement at wrist); 2 = moderate (movement at arm only, elbow or shoulder); and 3 = severe, generalized response or movement in more than one extremity, within ninety seconds. Any adverse effect due to these premedication agents was recorded. Results The incidence and intensity of myoclonus were significantly lower in the low-dose etomidate group. The incidence rates of myoclonus were 51 (71.85%), 61 (85.9%), 30 (42.3%) and 41 (57.7%), and the percentages of patients who experienced grade III of myoclonus were 30 (58.8%), 32 (52.5%), 9 (30%) and 14 (34.1%) in the midazolam, magnesium sulfate, etomidate and remifentanil groups, respectively. The incidence and intensity of myoclonus were significantly

  20. Adaptive-weighted total variation minimization for sparse data toward low-dose x-ray computed tomography image reconstruction

    NASA Astrophysics Data System (ADS)

    Liu, Yan; Ma, Jianhua; Fan, Yi; Liang, Zhengrong

    2012-12-01

    Previous studies have shown that by minimizing the total variation (TV) of the to-be-estimated image with some data and other constraints, piecewise-smooth x-ray computed tomography (CT) can be reconstructed from sparse-view projection data without introducing notable artifacts. However, due to the piecewise constant assumption for the image, a conventional TV minimization algorithm often suffers from over-smoothness on the edges of the resulting image. To mitigate this drawback, we present an adaptive-weighted TV (AwTV) minimization algorithm in this paper. The presented AwTV model is derived by considering the anisotropic edge property among neighboring image voxels, where the associated weights are expressed as an exponential function and can be adaptively adjusted by the local image-intensity gradient for the purpose of preserving the edge details. Inspired by the previously reported TV-POCS (projection onto convex sets) implementation, a similar AwTV-POCS implementation was developed to minimize the AwTV subject to data and other constraints for the purpose of sparse-view low-dose CT image reconstruction. To evaluate the presented AwTV-POCS algorithm, both qualitative and quantitative studies were performed by computer simulations and phantom experiments. The results show that the presented AwTV-POCS algorithm can yield images with several notable gains, in terms of noise-resolution tradeoff plots and full-width at half-maximum values, as compared to the corresponding conventional TV-POCS algorithm.

  1. Adaptive-weighted total variation minimization for sparse data toward low-dose x-ray computed tomography image reconstruction.

    PubMed

    Liu, Yan; Ma, Jianhua; Fan, Yi; Liang, Zhengrong

    2012-12-01

    Previous studies have shown that by minimizing the total variation (TV) of the to-be-estimated image with some data and other constraints, piecewise-smooth x-ray computed tomography (CT) can be reconstructed from sparse-view projection data without introducing notable artifacts. However, due to the piecewise constant assumption for the image, a conventional TV minimization algorithm often suffers from over-smoothness on the edges of the resulting image. To mitigate this drawback, we present an adaptive-weighted TV (AwTV) minimization algorithm in this paper. The presented AwTV model is derived by considering the anisotropic edge property among neighboring image voxels, where the associated weights are expressed as an exponential function and can be adaptively adjusted by the local image-intensity gradient for the purpose of preserving the edge details. Inspired by the previously reported TV-POCS (projection onto convex sets) implementation, a similar AwTV-POCS implementation was developed to minimize the AwTV subject to data and other constraints for the purpose of sparse-view low-dose CT image reconstruction. To evaluate the presented AwTV-POCS algorithm, both qualitative and quantitative studies were performed by computer simulations and phantom experiments. The results show that the presented AwTV-POCS algorithm can yield images with several notable gains, in terms of noise-resolution tradeoff plots and full-width at half-maximum values, as compared to the corresponding conventional TV-POCS algorithm.

  2. Low-dose cerebral perfusion computed tomography image restoration via low-rank and total variation regularizations

    PubMed Central

    Niu, Shanzhou; Zhang, Shanli; Huang, Jing; Bian, Zhaoying; Chen, Wufan; Yu, Gaohang; Liang, Zhengrong; Ma, Jianhua

    2016-01-01

    Cerebral perfusion x-ray computed tomography (PCT) is an important functional imaging modality for evaluating cerebrovascular diseases and has been widely used in clinics over the past decades. However, due to the protocol of PCT imaging with repeated dynamic sequential scans, the associative radiation dose unavoidably increases as compared with that used in conventional CT examinations. Minimizing the radiation exposure in PCT examination is a major task in the CT field. In this paper, considering the rich similarity redundancy information among enhanced sequential PCT images, we propose a low-dose PCT image restoration model by incorporating the low-rank and sparse matrix characteristic of sequential PCT images. Specifically, the sequential PCT images were first stacked into a matrix (i.e., low-rank matrix), and then a non-convex spectral norm/regularization and a spatio-temporal total variation norm/regularization were then built on the low-rank matrix to describe the low rank and sparsity of the sequential PCT images, respectively. Subsequently, an improved split Bregman method was adopted to minimize the associative objective function with a reasonable convergence rate. Both qualitative and quantitative studies were conducted using a digital phantom and clinical cerebral PCT datasets to evaluate the present method. Experimental results show that the presented method can achieve images with several noticeable advantages over the existing methods in terms of noise reduction and universal quality index. More importantly, the present method can produce more accurate kinetic enhanced details and diagnostic hemodynamic parameter maps. PMID:27440948

  3. Local application of low-dose insulin in improving wound healing after deep burn surgery

    PubMed Central

    Wang, Chejiang; Wang, Jiazhe; Feng, Jianke

    2016-01-01

    The clinical effects of local application of low-dose insulin in improving wound healing after deep burn self-skin transplantation surgery were examined. Fifty-eight patients with deep burns were selected and randomly divided into 3 groups. In the blank control group, normal saline was injected to the subcutaneous tissue of wounds; in large dose insulin group, 1.0 µ long-term suspended zinc insulin was locally injected; and in the low-dose insulin group, 0.1 µ long-term suspended zinc insulin was locally injected. The healing effects were compared. After 7 and 14 days of treatments, wound surface area in the low-dose group was significantly smaller than in the other groups, and differences were statistically significant (P<0.05); wound healing duration and infection rate for patients in the low-dose group were significantly lower, class A healing rate was significantly improved, and the differences were statistically significant (P<0.05). Insulin resistance index (HOMA-IR) in the low-dose group was significantly lower, insulin secretion index (HOMA-β) and the insulin sensitivity index (HOMA-ISI) significantly increased. The expression levels of vascular endothelial growth factor and tumor necrosis factor-α in local tissue for the low-dose group were significantly higher than those in the other two groups. Differences were statistically significant (P<0.05). In conclusion, local application of low-dose insulin can effectively improve wound healing after deep burn surgeries. PMID:27698753

  4. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

    PubMed Central

    Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

    2012-01-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  5. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.

    PubMed

    Vandenberg, Laura N; Colborn, Theo; Hayes, Tyrone B; Heindel, Jerrold J; Jacobs, David R; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M; vom Saal, Frederick S; Welshons, Wade V; Zoeller, R Thomas; Myers, John Peterson

    2012-06-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  6. Hemiablative Focal Low Dose Rate Brachytherapy: A Phase II Trial Protocol

    PubMed Central

    Bucci, Joseph; Chin, Yaw Sinn; Malouf, David; Howie, Andrew; Enari, Komiti Ese

    2016-01-01

    trial (RCT). Conclusions This protocol is designed to show feasibility in delivering hemigland focal therapy with seed BT. It may answer crucial questions and obtain data which will enable downstream decisions on focal low dose rate (LDR) prostate BT. ClinicalTrial Clinicaltrial.gov NCT02643511; https://www.clinicaltrials.gov/ct2/show/NCT02643511 (Archived by Webcite at http://www.webcitation.org/6ghLCzIhY) PMID:27296781

  7. Low dose tomographic fluoroscopy: 4D intervention guidance with running prior

    SciTech Connect

    Flach, Barbara; Kuntz, Jan; Brehm, Marcus; Kachelrieß, Marc; Kueres, Rolf; Bartling, Sönke

    2013-10-15

    . Reconstructed volumes based on the running prior show high image quality without introducing new artifacts and the interventional materials are displayed at the correct position.Conclusions: The running prior improves the robustness of low dose 3D+T intervention guidance toward intended or unintended patient motion.

  8. Body-wide anatomy recognition in PET/CT images

    NASA Astrophysics Data System (ADS)

    Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A.

    2015-03-01

    With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible.

  9. Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

    PubMed Central

    Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

    2016-01-01

    Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http

  10. Noise correlation in CBCT projection data and its application for noise reduction in low-dose CBCT

    SciTech Connect

    Zhang, Hua; Ouyang, Luo; Wang, Jing E-mail: jing.wang@utsouthwestern.edu; Ma, Jianhua E-mail: jing.wang@utsouthwestern.edu; Huang, Jing; Chen, Wufan

    2014-03-15

    Purpose: To study the noise correlation properties of cone-beam CT (CBCT) projection data and to incorporate the noise correlation information to a statistics-based projection restoration algorithm for noise reduction in low-dose CBCT. Methods: In this study, the authors systematically investigated the noise correlation properties among detector bins of CBCT projection data by analyzing repeated projection measurements. The measurements were performed on a TrueBeam onboard CBCT imaging system with a 4030CB flat panel detector. An anthropomorphic male pelvis phantom was used to acquire 500 repeated projection data at six different dose levels from 0.1 to 1.6 mAs per projection at three fixed angles. To minimize the influence of the lag effect, lag correction was performed on the consecutively acquired projection data. The noise correlation coefficient between detector bin pairs was calculated from the corrected projection data. The noise correlation among CBCT projection data was then incorporated into the covariance matrix of the penalized weighted least-squares (PWLS) criterion for noise reduction of low-dose CBCT. Results: The analyses of the repeated measurements show that noise correlation coefficients are nonzero between the nearest neighboring bins of CBCT projection data. The average noise correlation coefficients for the first- and second-order neighbors are 0.20 and 0.06, respectively. The noise correlation coefficients are independent of the dose level. Reconstruction of the pelvis phantom shows that the PWLS criterion with consideration of noise correlation (PWLS-Cor) results in a lower noise level as compared to the PWLS criterion without considering the noise correlation (PWLS-Dia) at the matched resolution. At the 2.0 mm resolution level in the axial-plane noise resolution tradeoff analysis, the noise level of the PWLS-Cor reconstruction is 6.3% lower than that of the PWLS-Dia reconstruction. Conclusions: Noise is correlated among nearest neighboring

  11. Low-dose performance of wafer-scale CMOS-based X-ray detectors

    NASA Astrophysics Data System (ADS)

    Maes, Willem H.; Peters, Inge M.; Smit, Chiel; Kessener, Yves; Bosiers, Jan

    2015-03-01

    Compared to published amorphous-silicon (TFT) based X-ray detectors, crystalline silicon CMOS-based active-pixel detectors exploit the benefits of low noise, high speed, on-chip integration and featuring offered by CMOS technology. This presentation focuses on the specific advantage of high image quality at very low dose levels. The measurement of very low dose performance parameters like Detective Quantum Efficiency (DQE) and Noise Equivalent Dose (NED) is a challenge by itself. Second-order effects like defect pixel behavior, temporal and quantization noise effects, dose measurement accuracy and limitation of the x-ray source settings will influence the measurements at very low dose conditions. Using an analytical model to predict the low dose behavior of a detector from parameters extracted from shot-noise limited dose levels is presented. These models can also provide input for a simulation environment for optimizing the performance of future detectors. In this paper, models for predicting NED and the DQE at very low dose are compared to measurements on different CMOS detectors. Their validity for different sensor and optical stack combinations as well as for different x-ray beam conditions was validated.

  12. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    SciTech Connect

    Gilbert, E.S.

    1993-04-01

    The main objective of radiation risk assessment is to determine the risk of various adverse health effects associated with exposure to low doses and low dose rates. Extrapolation of risks from studies of persons exposed at high doses (generally exceeding 1 Sv) and dose rates has been the primary approach used to achieve this objective. The study of Japanese atomic bomb survivors in Hiroshima and Nagasaki has played an especially important role in risk assessment efforts. A direct assessment of the dose-response function based on studies of persons exposed at low doses and dose rates is obviously desirable. This paper focuses on the potential of both current and future nuclear workers studies for investigating the dose-response functions at low doses, and also discusses analyses making use of the low dose portion of the atomic bomb survivor data. Difficulties in using these data are the statistical imprecision of estimated dose-response parameters, and potential bias resulting from confounding factors and from uncertainties in dose estimates.

  13. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    PubMed

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance. PMID:25595209

  14. Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments.

    PubMed

    Izadifar, Zohreh; Honaramooz, Ali; Wiebe, Sheldon; Belev, George; Chen, Xiongbiao; Chapman, Dean

    2016-03-01

    In tissue engineering, non-invasive imaging of biomaterial scaffolds and tissues in living systems is essential to longitudinal animal studies for assessments without interrupting the repair process. Conventional X-ray imaging is inadequate for use in soft tissue engineering due to the limited absorption difference between the soft tissue and biomaterial scaffolds. X-ray phase-based imaging techniques that derive contrast from refraction or phase effects rather than absorption can provide the necessary contrast to see low-density biomaterial scaffolds and tissues in large living systems. This paper explores and compares three synchrotron phase-based X-ray imaging techniques-computed tomography (CT)-diffraction enhanced imaging (DEI), -analyzer based imaging (ABI), and -phase contrast imaging (PCI)-for visualization and characterization of low-density biomaterial scaffolds and tissues in situ for non-invasive soft tissue engineering assessments. Intact pig joints implanted with polycaprolactone scaffolds were used as the model to assess and compare the imaging techniques in terms of different qualitative and quantitative criteria. For long-term in vivo live animal imaging, different strategies for reducing the imaging radiation dose and scan time-reduced number of CT projections, region of interest, and low resolution imaging-were examined with the presented phase-based imaging techniques. The results demonstrated promising capabilities of the phase-based techniques for visualization of biomaterial scaffolds and soft tissues in situ. The low-dose imaging strategies were illustrated effective for reducing the radiation dose to levels appropriate for live animal imaging. The comparison among the imaging techniques suggested that CT-DEI has the highest efficiency in retaining image contrast at considerably low radiation doses.

  15. [The effect of low dose gestagens on the hypothalamic-pituitary-ovarian axis].

    PubMed

    Friedrich, E

    1977-08-01

    The contraceptive effect of continuous treatment with low dose progestogens (minipill) has been attributed mainly to alterations of the cervical mucus and the endometrium. This study was undertaken to investigate the effect of low dose progestogens on hypothalamic-pituitary-ovarian function. Plasma concentrations of follicle stimulating hormone (FSH), luteininzing hormone (LH), estradiol-17 beta (E-2) and Progesterone were measured daily during apparently ovulatory menstrual cycles and during treatment cycles with different low dose progestogens. From the results obtained it was concluded that the minipill has a clear-cut effect on the LH/FSH peak at midcycle and on corpus luteum function. A cyclic secretion of E-2 is maintained in the majority of cases. In a few treatment cycles however, follicular maturation was suppressed as indicated by low E-2 concentrations. It was concluded that the minipill exerts a profound effect at the central and ovarian level which contributes to its satisfactory contraceptive efficacy.

  16. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  17. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    SciTech Connect

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  18. Data integration reveals key homeostatic mechanisms following low dose radiation exposure

    SciTech Connect

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-15

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time — with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24–72 h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. - Highlights: • Low dose ionizing radiation altered homeostasis in 3D skin tissue model. • Global gene/protein/metabolite data integrated using complementary statistical approaches • Time and location-specific change in matrix regulation

  19. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    SciTech Connect

    Shin, Suk Chul; Lee, Kyung-Mi; Kang, Yu Mi; Kim, Kwanghee; Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo; Kim, Chong Soon; Kim, Hee Sun

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  20. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    SciTech Connect

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  1. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    NASA Astrophysics Data System (ADS)

    Acheva, A.; Georgieva, R.; Rupova, I.; Boteva, R.; Lyng, F.

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  2. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid.

    PubMed

    Haastrup, Peter Fentz; Grønlykke, Thor; Jarbøl, Dorte Ejg

    2015-03-01

    Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric-coated ASA has been developed to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric-coated formulations. Therefore, low-dose enteric-coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.

  3. Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

    PubMed Central

    García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

    2016-01-01

    Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

  4. Oral and Conjunctival Exposure of Nonhuman Primates to Low Doses of Ebola Makona Virus

    PubMed Central

    Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Deer, Daniel J.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Nonhuman primate (NHP) models of Ebola virus (EBOV) infection primarily use parenteral or aerosol routes of exposure. Uniform lethality can be achieved in these models at low doses of EBOV (≤100 plaque-forming units [PFU]). Here, we exposed NHPs to low doses of EBOV (Makona strain) by the oral or conjunctival routes. Surprisingly, animals exposed to 10 PFU by either route showed no signs of disease. Exposure to 100 PFU resulted in illness and/or lethal infection. These results suggest that these more natural routes require higher doses of EBOV to produce disease or that there may be differences between Makona and historical strains. PMID:27284090

  5. Low-dose X-ray computed tomography image reconstruction with a combined low-mAs and sparse-view protocol.

    PubMed

    Gao, Yang; Bian, Zhaoying; Huang, Jing; Zhang, Yunwan; Niu, Shanzhou; Feng, Qianjin; Chen, Wufan; Liang, Zhengrong; Ma, Jianhua

    2014-06-16

    To realize low-dose imaging in X-ray computed tomography (CT) examination, lowering milliampere-seconds (low-mAs) or reducing the required number of projection views (sparse-view) per rotation around the body has been widely studied as an easy and effective approach. In this study, we are focusing on low-dose CT image reconstruction from the sinograms acquired with a combined low-mAs and sparse-view protocol and propose a two-step image reconstruction strategy. Specifically, to suppress significant statistical noise in the noisy and insufficient sinograms, an adaptive sinogram restoration (ASR) method is first proposed with consideration of the statistical property of sinogram data, and then to further acquire a high-quality image, a total variation based projection onto convex sets (TV-POCS) method is adopted with a slight modification. For simplicity, the present reconstruction strategy was termed as "ASR-TV-POCS." To evaluate the present ASR-TV-POCS method, both qualitative and quantitative studies were performed on a physical phantom. Experimental results have demonstrated that the present ASR-TV-POCS method can achieve promising gains over other existing methods in terms of the noise reduction, contrast-to-noise ratio, and edge detail preservation.

  6. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    SciTech Connect

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  7. Diuretic downsides--but in low doses they still seem among the best authenticated antihypertensives.

    PubMed

    Opie, L H

    2000-08-01

    Diuretics in low doses have the greatest support among current available antihypertensives in that they have been shown to reduce total mortality, coronary mortality, stroke, and congestive heart failure in an important meta-analysis by Psaty. Recently, Messerli has linked longterm diuretic use to renal cell carcinoma in women. In some patients, diuretic use leads to increasing blood cholesterol and blood sugar levels. Impotence is a recognized side effect, with rates rising about twofold with low-dose chlorthalidone and fourfold with a higher dose. Certain population groups such as younger (<60 years) white males often do not respond to low-dose diuretic therapy with an adequate blood pressure fall. In females of a similar age group, Messerli calculates that prolonged diuretic therapy will prevent only one stroke and no coronary events nor any deaths for every renal cell carcinoma that is provoked. Despite these evident problems, the outcome data on hard endpoints in trials with initial low-dose diuretic therapy remain valid and convincing. Thus, it is argued, low- but not high-dose diuretics retain their primacy in the ranking of antihypertensive therapy.

  8. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 ± 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

  9. Low dose heparin: bleeding and wound complications in the surgical patient. A prospective randomized study.

    PubMed Central

    Pachter, H L; Riles, T S

    1977-01-01

    A randomized prospective study of low dose heparin was performed in 175 surgical patients to determine the frequency of bleeding and wound complications. The patients were divided into three groups: (1) low dose heparin (5000 units two hours before operation and 5000 units every 12 hours following operation for five days); (2) low dose heparin postoperatively only; and (3) a control group. The frequency of bleeding and wound complications was 27% in group I, 7.5% in group II, and 1.4% in group III. The difference between the control patients and those heparinized pre- and postoperatively is statistically significant (p less than 0.005). None of the patients in any of the three groups had a pulmonary embolus, but the number of patients involved is too small to assess the significance of this finding. However, a bleeding and wound complication rate of 27% is significant. These findings indicate that perhaps the routine use of low dose heparin should be reserved for those patients with preoperative factors indicating an increased risk from thromboembolism. PMID:603271

  10. Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia.

    PubMed

    Zhou, Hai; Hou, Yu; Liu, Xuena; Qiu, Jihua; Feng, Qi; Wang, Yawen; Zhang, Xu; Min, Yanan; Shao, Linlin; Liu, Xinguang; Li, Guosheng; Li, Lizhen; Yang, Lei; Xu, Shuqian; Ni, Heyu; Peng, Jun; Hou, Ming

    2015-05-01

    Impaired megakaryocyte maturation and insufficient platelet production have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our previous study demonstrated that low expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to promote cell differentiation and maturation at low doses. However, whether decitabine is potential in promoting megakaryocyte maturation and platelet release in ITP is unclear. In this study, we evaluated the effect of DAC on megakaryocyte maturation and platelet release in the presence of ITP plasma that has been shown to cause impaired megakaryocyte maturation and platelet production. We observed that low-dose DAC (10 nM) could significantly increase the number of mature polyploid (≥ 4N) megakaryocytes in cultures with plasma from healthy controls and more than one-half of ITP patients in vitro. Furthermore, the number of platelets released from these megakaryocytes significantly increased compared with those untreated with DAC. In these megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its promoter methylation status. These findings demonstrate that low-dose DAC can promote megakaryocyte maturation and platelet production and enhance TRAIL expression in megakaryocytes in healthy controls and ITP. The potential therapeutic role of low-dose DAC may be beneficial for thrombocytopenic disorders.

  11. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  12. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  13. 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…

  14. Acute, Low-dose CO Inhalation does not Alter Energy Expenditure during Submaximal Exercise.

    PubMed

    Kane, L A; Ryan, B J; Schmidt, W; Byrnes, W C

    2016-01-01

    Carbon monoxide, a gas known most widely for its toxic effects at high doses, is receiving increased attention for its role as a physiological signaling molecule and potential therapeutic agent when administered in low doses. We sought to quantify any changes to oxygen consumption and energy expenditure during submaximal exercise after low-dose CO inhalation. 9 active individuals completed 4 graded submaximal exercise tests, with each test occurring during a separate visit. For their first exercise test, subjects inhaled CO or room air (1.2 mL·kg(-1) body mass) in a randomized, subject-blind fashion. A second test was repeated 24 h later when the inhaled gas should have cleared the system. Subjects repeated study procedures with the alternate dose after a washout period of at least 2 days. Low-dose CO administration did not affect oxygen consumption or energy expenditure during submaximal exercise immediately or 24 h following its administration. Increases in heart rate, blood [lactate], and perceived exertion were observed following acute CO inhalation but these effects were absent after 24 h. The results of this study suggest that low-dose CO administration does not influence the energetics of submaximal exercise, but it acutely increases the relative intensity associated with absolute workloads below the lactate threshold.

  15. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    PubMed

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

  16. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

    PubMed Central

    Zhang, Yin; Yang, Yunlong; Hosaka, Kayoko; Huang, Guichun; Zang, Jingwu; Chen, Fang; Zhang, Yun; Samani, Nilesh J.; Cao, Yihai

    2016-01-01

    Anti-VEGF–based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects. PMID:27035988

  17. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    PubMed

    Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

  18. Effects of acute low doses of gamma-radiation on erythrocytes membrane.

    PubMed

    Mahmoud, Sherif S; El-Sakhawy, Eman; Abdel-Fatah, Eman S; Kelany, Adel M; Rizk, Rizk M

    2011-03-01

    It is believed that any dose of ionizing radiation may damage cells and that the mutated cells could develop into cancer cells. Additionally, results of research performed over the past century on the effects of low doses of ionizing radiation on biological organisms show beneficial health effects, called hormesis. Much less is known about the cellular response to low doses of ionizing radiation, such as those typical for medical diagnostic procedures, normal occupational exposures or cosmic-ray exposures at flight altitudes. Extrapolating from the effects observed at higher doses to predict changes in cells after low-dose exposure is problematic. We examined the biological effects of low doses (0.01-0.3 Gy) of γ-radiation on the membrane characteristics of erythrocytes of albino rats and carried out osmotic fragility tests and Fourier transform infrared spectroscopy (FTIR). Our results indicate that the lowest three doses in the investigated radiation range, i.e., 0.01, 0.025 and 0.05 Gy, resulted in positive effects on the erythrocyte membranes, while a dose of 0.1 Gy appeared to represent the limiting threshold dose of those positive effects. Doses higher than 0.1 Gy were associated with the denaturation of erythrocyte proteins. PMID:20865271

  19. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  20. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    PubMed

    Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods. PMID:27447827

  1. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    PubMed

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

  2. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

    PubMed Central

    Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

    2014-01-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

  3. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    PubMed Central

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

  4. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment

    PubMed Central

    Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Kirschke, Jan S.; Noël, Peter B.

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods. PMID:27447827

  5. Complete resolution of clozapine-induced sialorrhea with low dose trihexyphenidyl.

    PubMed

    Praharaj, Samir Kumar; Sarkhel, Sujit; Khanande, Roshan Vitthalrao; Sinha, Vinod Kumar

    2010-01-01

    Clozapine-induced sialorrhea (CIS) is a frequently occurring debilitating adverse effect. Although various treatment options exist, none has been proved to be distinctly superior to others. We report a case of CIS that responded to low dose of trihexyphenidyl (2 mg/day).

  6. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    EPA Science Inventory

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?

    Abstract
    High doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  7. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation

    PubMed Central

    Zhao, Yuchao; Ricci, Paolo F.

    2010-01-01

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health. PMID:21191485

  8. Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

    PubMed Central

    Casali, Karina Rabello; Baraldi, Dhãniel; Conzatti, Adriana; Araújo, Alex Sander da Rosa; Khaper, Neelam; Llesuy, Susana; Rigatto, Katya; Belló-Klein, Adriane

    2014-01-01

    This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n = 9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy. PMID:24738017

  9. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy.

    PubMed

    Zhang, Yin; Yang, Yunlong; Hosaka, Kayoko; Huang, Guichun; Zang, Jingwu; Chen, Fang; Zhang, Yun; Samani, Nilesh J; Cao, Yihai

    2016-04-12

    Anti-VEGF-based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects.

  10. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  11. Low-dose carbon monoxide inhalation protects neuronal cells from apoptosis after optic nerve crush.

    PubMed

    Chen, Zeli; Wang, Ruobing; Wu, Jiangchun; Xia, Fangzhou; Sun, Qinglei; Xu, Jiajun; Liu, Lin

    2016-01-22

    Glaucomatous optic neuropathy, including axonal degeneration and apoptotic death of retinal ganglion cells (RGCs), eventually leads to irreversible visual impairment. Carbon monoxide (CO) acts as a therapeutic agent against neural injury via its anti-apoptotic effect. Here we hypothesized that low-dose CO inhalation can protect RGCs in a rat model of optic nerve crush (ONC). ONC was performed on adult male Sprague Dawley rats to imitate glaucomatous optic damage. Low-dose CO (250 ppm) or air was inhaled for 1 h immediately after ONC, and all the tests were carried out 2 weeks later. Flash visual evoked potentials (FVEP) and pupil light relax (PLR) were recorded for the assessment of visual function. RGC density was evaluated by hematoxylin and eosin staining and Fluorogold labeling. Retinal apoptotic process was assessed by TUNEL staining and caspase-3 activity measurement. Low-dose CO treatment significantly ameliorated the abnormalities of FVEP and PLR induced by ONC. As expected, the RGC density was increased remarkably by CO inhalation after the glaucomatous optic nerve insult. Moreover, CO treatment after ONC significantly decreased the number of TUNEL-positive cells in ganglion cell layer and attenuated the retinal caspase-3 activity. Low-dose CO inhalation protects RGCs from optic nerve injury via inhibiting caspase-3 dependent apoptosis.

  12. The prevalence of intolerance for low-dose acetylsalicylacid in the secondary prevention of atherothrombosis.

    PubMed

    Tournoij, E; Peters, R J G; Langenberg, M; Kanhai, K J K; Moll, F L

    2009-05-01

    Daily low-dose acetylsalicylacid (ASA) is prescribed to patients with atherothrombosis frequently to prevent vascular complications. In reports on complications and side effects of low-dose ASA use in the literature there is a range of definitions. We explored the incidence, characteristics and consequences of symptoms suggestive of ASA intolerance in patients on low-dose ASA. General practitioners and specialists in 105 centres were asked to review their patient files for the last 10 consecutive patients who were prescribed ASA. Participating patients completed a questionnaire about their current ASA use (doctors completed the questionnaire together with the patients), use of co-medication and symptoms suggestive of ASA intolerance. A total of 947 patients were included in this study. Sixty patients (6.6%) had ceased ASA treatment, predominantly because of the occurrence of side effects suspected to be caused by ASA use. A quarter of the patients concomitantly used an anti-acid agent. Of the 947 patients, 271 (30.6%) indicated symptoms during ASA intake. The most common symptoms were related to the gastrointestinal tract (25.1%). In patients prescribed a low-dose of ASA monotherapy, side effects suggestive of intolerance are common. More awareness should be created to detect and treat these symptoms, because the occurrence of side effects is the most important reason for patients to discontinue ASA treatment. PMID:19297216

  13. Implications for human and environmental health of low doses of ionising radiation.

    PubMed

    Mothersill, Carmel; Seymour, Colin

    2014-07-01

    The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed.

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

    PubMed

    Leenhouts, H P; Chadwick, K H

    2011-03-01

    This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations. PMID:21346287

  15. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials

    PubMed Central

    Charlebois, Audrey; Jacques, Mario; Archambault, Marie

    2014-01-01

    Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. PMID:24795711

  16. Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

    PubMed

    Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

    2015-12-01

    Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks. PMID:26038159

  17. Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

    PubMed

    Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

    2015-12-01

    Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

  18. Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

    SciTech Connect

    Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.; Le, Quynh-Thu; Hoppe, Richard T.; Donaldson, Sarah S.

    2013-08-01

    Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

  19. Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

    SciTech Connect

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

    2014-07-29

    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  20. Costs, benefits and redundant mechanisms of adaption to chronic low-dose stress in yeast

    PubMed Central

    Markiewicz-Potoczny, Marta; Lydall, David

    2016-01-01

    ABSTRACT All organisms live in changeable, stressful environments. It has been reported that exposure to low-dose stresses or poisons can improve fitness. However, examining the effects of chronic low-dose chemical exposure is challenging. To address this issue we used temperature sensitive mutations affecting the yeast cell division cycle to induce low-dose stress for 40 generation times, or more. We examined cdc13-1 mutants, defective in telomere function, and cdc15-2 mutants, defective in mitotic kinase activity. We found that each stress induced similar adaptive responses. Stress-exposed cells became resistant to higher levels of stress but less fit, in comparison with unstressed cells, in conditions of low stress. The costs and benefits of adaptation to chronic stress were reversible. In the cdc13-1 context we tested the effects of Rad9, a central player in the response to telomere defects, Exo1, a nuclease that degrades defective telomeres, and Msn2 and Msn4, 2 transcription factors that contribute to the environmental stress response. We also observed, as expected, that Rad9 and Exo1 modulated the response of cells to stress. In addition we observed that adaptation to stress could still occur in these contexts, with associated costs and benefits. We conclude that functionally redundant cellular networks control the adaptive responses to low dose chronic stress. Our data suggests that if organisms adapt to low dose stress it is helpful if stress continues or increases but harmful should stress levels reduce. PMID:27628486

  1. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

    SciTech Connect

    Chen, Xian

    2013-10-23

    The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information, we will perform a computational network analysis to elucidate a global pathway/mechanisms underlying cellular responses to real-time low-dose IR. Similarly, we will extend our scheme to investigate systematically those induction/transmission pathways occurring in a fibroblast-epithelial interacting model in which the bystander cell (fibroblast) monitor the IR damage to the target cell (epithelial cell). The results will provide the proteome base (molecular mechanisms/pathways for signaling) for the low dose radiation-induced essential tissue

  2. Resource utilization. High dose rate versus low dose rate brachytherapy for gynecologic cancer.

    PubMed

    Bastin, K; Buchler, D; Stitt, J; Shanahan, T; Pola, Y; Paliwal, B; Kinsella, T

    1993-06-01

    A comparative analysis of anesthesia use, perioperative morbidity and mortality, capital, and treatment cost of high dose rate versus low dose rate intracavitary brachytherapy for gynecologic malignancy is presented. To assess current anesthesia utilization, application location, and high dose rate afterloader availability for gynecologic brachytherapy in private and academic practices, a nine-question survey was sent to 150 radiotherapy centers in the United States, of which 95 (63%) responded. Of these 95 respondents, 95% used low dose rate brachytherapy, and 18% possessed high dose rate capability. General anesthesia was used in 95% of programs for tandem + ovoid and in 31% for ovoids-only placement. Differences among private and academic practice respondents were minimal. In our institution, a cost comparison for low dose rate therapy (two applications with 3 hospital days per application, operating and recovery room use, spinal anesthesia, radiotherapy) versus high dose rate treatment (five outpatient departmental applications, intravenous anesthesia without an anesthesiologist, radiotherapy) revealed a 244% higher overall charge for low dose rate treatment, primarily due to hospital and operating room expenses. In addition to its ability to save thousands of dollars per intracavitary patient, high dose rate therapy generated a "cost-shift," increasing radiotherapy departmental billings by 438%. More importantly, perioperative morbidity and mortality in our experience of 500+ high dose rate applications compared favorably with recently reported data using low dose rate intracavitary treatment. Capital investment, maintenance requirements, and depreciation costs for high dose rate capability are reviewed. Application of the defined "revenue-cost ratio" formula demonstrates the importance of high application numbers and consistent reimbursement for parity in high dose rate operation. Logically, inadequate third-party reimbursement (e.g., Medicare) reduces high

  3. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice

    PubMed Central

    Go, Young-Mi; Sutliff, Roy L.; Chandler, Joshua D.; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A.; Orr, Michael; Hao, Li; Fowler, Bruce A.; Jones, Dean P.

    2015-01-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd–treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis. PMID:26187450

  4. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice.

    PubMed

    Go, Young-Mi; Sutliff, Roy L; Chandler, Joshua D; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A; Orr, Michael; Hao, Li; Fowler, Bruce A; Jones, Dean P

    2015-10-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd-treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis.

  5. Implications for human and environmental health of low doses of ionising radiation.

    PubMed

    Mothersill, Carmel; Seymour, Colin

    2014-07-01

    The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed. PMID:23664231

  6. Continuous Low-Dose Temozolomide Chemotherapy and Microvessel Density in Recurrent Glioblastoma

    PubMed Central

    Woo, Jong-Yun; Yang, Seung Ho; Lee, Youn Soo; Lee, Su Youn; Kim, Jeana

    2015-01-01

    Objective The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. Methods Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m2/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). Results The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was 22.7±24.1/mm2 (mean±standard deviation), and this was lower than that of the initial tumor (61.4±32.7/mm2) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. Conclusion The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM. PMID:26713142

  7. Long term outcome and side effects in patients receiving low-dose I125 brachytherapy: a retrospective analysis

    PubMed Central

    Logghe, Pieter; Verlinde, Rolf; Bouttens, Frank; den Broecke, Caroline Van; Deman, Nathalie; Verboven, Koen; Maes, Dirk; Merckx, Luc

    2016-01-01

    ABSTRACT Objectives: To retrospectively evaluate the disease free survival (DFS), disease specific survival (DSS),overall survival (OS) and side effects in patients who received low-dose rate (LDR) brachytherapy with I125 stranded seeds. Materials and methods: Between july 2003 and august 2012, 274 patients with organ confined prostate cancer were treated with permanent I125 brachytherapy. The median follow-up, age and pretreatment prostate specific antigen (iPSA) was 84 months (12-120), 67 years (50-83) and 7.8 ng/mL (1.14-38), respectively. Median Gleason score was 6 (3-9). 219 patients (80%) had stage cT1c, 42 patients (15.3%) had stage cT2a, 3 (1.1%) had stage cT2b and 3 (1.1%) had stage cT2c. The median D90 was 154.3 Gy (102.7-190.2). Results: DSS was 98.5%.OS was 93.5%. 13 patients (4.7%) developed systemic disease, 7 patients (2.55%) had local progression. In 139 low risk patients, the 5 year biochemical freedom from failure rate (BFFF) was 85% and 9 patients (6.4%) developed clinical progression. In the intermediate risk group, the 5 year BFFF rate was 70% and 5 patients (7.1%) developed clinical progression. Median nPSA in patients with biochemical relapse was 1.58 ng/mL (0.21 – 10.46), median nPSA in patients in remission was 0.51 ng/mL (0.01 – 8.5). Patients attaining a low PSA nadir had a significant higher BFFF (p<0.05). Median D90 in patients with biochemical relapse was 87.2 Gy (51 – 143,1). Patients receiving a high D90 had a significant higher BFFF (p<0.05). Conclusion: In a well selected patient population, LDR brachytherapy offers excellent outcomes. Reaching a low PSA nadir and attaining high D90 values are significant predictors for a higher DFS. PMID:27532118

  8. Final Report - Epigenetics of low dose radiation effects in an animal model

    SciTech Connect

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low

  9. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients.

    PubMed

    Wu, Huang-Pin; Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  10. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients

    PubMed Central

    Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  11. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    SciTech Connect

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better

  12. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

    PubMed

    Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

    2016-02-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin.

  13. Evaluation of body composition during low-dose estrogen oral contraceptives treatment.

    PubMed

    Franchini, M; Caruso, C; Nigrelli, S; Poggiali, C

    1995-01-01

    The effect of two low-dose oral contraceptives (OCs) on weight and body composition was evaluated in 80 family planning clinic outpatients 18-43 years of age. These women were randomly assigned to receive OCs containing either 20 mcg ethinyl estradiol and 150 mcg desogestrel or 30 mcg ethinyl estradiol and 75 mcg gestodene. 20 IUD users served as controls. Anthropometric measurements and body composition (estimated by Bioelectrical Impedance Analysis) were assessed at baseline and after 6 and 12 months of OC use. In all three groups, body weight, body mass index, total body water, and body cellular mass remained unchanged during the 12-month study period. These findings confirm that the new low-dose OCs have no significant effects on body weight or composition.

  14. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature.

    PubMed

    Kulkarni, Ranganath R

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.

  15. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    PubMed

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  16. [Treatment of erosive gastropathy caused by nonsteroidal anti-inflammatory agents using low doses of antacids].

    PubMed

    Rybár, I; Rovenský, J; Orlovská, M

    2000-10-01

    In an open clinical, endoscopy controlled study involving 31 patients with erosive NSAIDs-induced gastropathy without Helicobacter pylori infection, the effect of low dose of antacids (120 mmol/l) with aluminium oxide and magnesium oxide (Maalox) administered for 4 weeks was followed. The administration of NSAIDs was not interrupted during the time of treatment. Healing rate of the gastric erosions after four weeks reached 65% (20/31) and endoscopic score in the gastric mucosa proved significant improvement (0.97 +/- 0.49 compared to 0.07 +/- 0.25, p < 0.01). Our results suggest efficacy of low dose antacids containing aluminium in the treatment of NSAIDs-induced gastric erosions.

  17. Issues in low dose radiation biology: the controversy continues. A perspective.

    PubMed

    Morgan, William F; Bair, William J

    2013-05-01

    Both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. Much of this is unavoidable, e.g., natural background radiation, but as the use of radiation increases, so does the potential health risk and the public's concerns. This perspective reflects the authors' view of current issues in low dose radiation biology research, highlights some of the controversies therein, and suggests areas of future research to address both issues in low dose radiation research and the controversies. This is a critical time for the radiation sciences and the implications of future research will have a significant impact on radiation protection, medicine, national security, research and industry. The views expressed here are the authors' own and do not represent any institution, organization or funding body.

  18. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  19. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature

    PubMed Central

    Kulkarni, Ranganath R.

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  20. [Specific long-term cellular changes under effects of low doses of radiation].

    PubMed

    Bychkovskaia, I B; Stepanov, R P; Fedortseva, R F

    2002-01-01

    We examined the peculiar form of a tissue postirradiative reaction characterizing by massive, dose-independent transition of cell populations to the steady state modification with the essential raise of cell damage and cell loss probability as compared with the probability level of the same alterations in controls. We described some other signs of such type of cellular transformation. It was found that the indicated cellular condition occurred both in active and slowly proliferating tissues. The reaction occurred at relatively low doses of irradiation. Some nonmutagenic factors also may evoke such effects. Our experimental data allow us to suppose the epigenetic mechanizms taking part in the induction and preservation of such alterations. The discovered form of cellular reaction manifestating in different biological objects may be considered as some general biological tendency. The importance of the studied reaction in the pathogenesis of late consequences of low dose irradiation is discussed. PMID:11898627

  1. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs

    PubMed Central

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-01-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH. PMID:23997262

  2. Evaluation of low-dose irradiation on microbiological quality of white carrots and string beans

    NASA Astrophysics Data System (ADS)

    Koike, Amanda C. R.; Santillo, Amanda G.; Rodrigues, Flávio T.; Duarte, Renato C.; Villavicencio, Anna Lucia C. H.

    2012-08-01

    The minimally processed food provided the consumer with a product quality, safety and practicality. However, minimal processing of food does not reduce pathogenic population of microorganisms to safe levels. Ionizing radiation used in low doses is effective to maintain the quality of food, reducing the microbiological load but rather compromising the nutritional values and sensory property. The association of minimal processing with irradiation could improve the quality and safety of product. The purpose of this study was to evaluate the effectiveness of low-doses of ionizing radiation on the reduction of microorganisms in minimally processed foods. The results show that the ionizing radiation of minimally processed vegetables could decontaminate them without several changes in its properties.

  3. Hepatocellular carcinoma stem cell-like cells are enriched following low-dose 5-fluorouracil chemotherapy

    PubMed Central

    Zhan, Yongqiang; Mou, Lisha; Cheng, Kangwen; Wang, Chengyou; Deng, Xuesong; Chen, Junren; Fan, Zhibing; Ni, Yong

    2016-01-01

    It has been proposed that cancer stem cells (CSCs) are involved in tumor resistance to chemotherapy and tumor relapse. The goal of the present study was to determine the effect of low-dose 5-fluorouracil (5-Fu) on enriched hepatocellular CSC-like cells. Increased cell motility and epithelial-mesenchymal transition were observed by migration assay in human hepatoblastoma PLC/RAF/5 cells following 5-Fu treatment, as well as a significant enhancement in their sphere-forming abilities. CSC-like cells were identified by side population cell analysis. The percentage of CSC-like cells in the surviving cells was greatly increased in response to 5-Fu. These findings indicate that low-dose 5-Fu treatment may efficiently enrich the CSC-like cell population in PLC/RAF/5 cells.

  4. Low-dose radioisotope scanning and quantitative analysis in the diagnosis of congenital hypothyroidism.

    PubMed Central

    O'Connor, M K; Freyne, P J; Cullen, M J

    1982-01-01

    Quantitative thyroid scanning using low doses of 99mTc sodium pertechnetate (1.85-3.7 MBq) was performed in 38 cases of congenital hypothyroidism. Of these 38 cases, 29 were scanned at 14 +/- 6 days old, and 9 at 1 year old. The scans show the full range of gland anatomy from athyreotic to normal. All morphologically normal scans had grossly increased uptakes of 99mTc. The incidence of the various thyroid anatomies was different in each age group. The average radiation dose to the thyroid was 2.29 mGy, with at least 70% of patients receiving a dose of 3.0 mGy or less. Such low doses of 99mTc should allow further scanning in later life. Neonatal thyroid scanning reveals the aetiology of congenital hypothyroidism and enables the clinician to assess the short- and long-term needs of the child. Images Fig. 1 PMID:6285837

  5. Ventilatory effects of low-dose paraoxon result from central muscarinic effects

    SciTech Connect

    Houze, Pascal; Pronzola, Laetita; Kayouka, Maya; Villa, Antoine; Debray, Marcel; Baud, Frederic J.

    2008-12-01

    Paraoxon induces respiratory toxicity. Atropine completely reversed parathion- and paraoxon-induced respiratory toxicity. The aim of this study was to assess the peripheral or central origin of ventilatory effects of low-dose paraoxon. Male Sprague-Dawley rats were given paraoxon 0.215 mg/kg subcutaneously and treated with either atropine (10 mg/kg sc) or ascending doses of methylatropine of 5.42 (equimolar to that of atropine), 54.2, and 542 mg/kg administered subcutaneously 30 min after paraoxon. Ventilation at rest was assessed using whole-body plethysmography and rat temperature using infra-red telemetry. Results are expressed as mean {+-} SE. Statistical analysis used two-way ANOVA for repeated measurements. Paraoxon induced a significant decrease in temperature 30 min after injection lasting the 90 min of the study period. This effect was partially corrected by atropine, but not by methylatropine whatever the dose. Paraoxon induced a decrease in respiratory rate resulting from an increase in expiratory time associated with an increase in tidal volume. Atropine completely reversed the ventilatory effects of low-dose paraoxon while the equimolar dose of methylatropine had no significant effects. The 54.2 and 542 mg/kg doses of methylatropine had no significant effects. Atropine crosses the blood-brain barrier and reverses peripheral and central muscarinic effects. In contrast, methylatropine does not cross the blood-brain barrier. Atropine completely reversed the ventilatory effects of low-dose paraoxon, while methylatropine had no significant effects at doses up to 100-fold the equimolar dose of atropine. We conclude that the ventilatory effects of low-dose paraoxon are mediated by disrupted muscarinic signaling in the central nervous system.

  6. Death due to fulminant neuroleptic malignant syndrome induced by low doses of haloperidol: a rare case.

    PubMed

    Zou, Donghua; Shao, Yu; Qin, Zhiqiang; Zhang, Jianhua; Liu, Ningguo; Li, Zhengdong; Huang, Ping; Chen, Yijiu

    2014-05-01

    The paper reports on a rare case of fulminant neuroleptic malignant syndrome (NMS) with several risk factors, typical manifestation and rapid death induced by low doses of haloperidol. The pathological findings, pathogenesis, clinical manifestations, diagnostic criteria, risk factors and other features of NMS are discussed. The importance of forensic pathologists being aware of the possibility of NMS as the cause of death in people taking antipsychotic drugs is stressed. PMID:24794843

  7. Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.

    PubMed

    Alburges, Mario E; Hoonakker, Amanda J; Cordova, Nathaniel M; Robson, Christina M; McFadden, Lisa M; Martin, Amber L; Hanson, Glen R

    2015-08-01

    Administration of methamphetamine (METH) alters limbic-related (LR) neurotensin (NT) systems. Thus, through a D1-receptor mechanism, noncontingent high doses (5-15 mg kg(-1)), and likely self-administration, of METH appears to reduce NT release causing its accumulation and an elevation of NT-like immunoreactivity (NTLI) in limbic-related NT pathways. For comparison, we tested the effect of low doses of METH, that are more like those used in therapy, on NTLI in the core and shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg). METH at the dose of 0.25 mg kg(-1) in particular, but not 1.00 mg kg(-1), decreased NTLI concentration in all of the LR structures studied, except for the prefrontal cortex; however, these effects were rapid and brief being observed at 5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels were reduced after the low dose of METH, the effect was blocked by pretreatment with either a D1 or a D2 antagonist. Thus, opposite to high doses like those associated with abuse, the therapeutic-like low-dose METH treatment induced reduction in NT tissue levels likely reflected an increase in NT release and a short-term depletion of the levels of this neuropeptide in LR structures, manifesting features comparable to the response of basal ganglia NT systems to similar low doses of METH.

  8. Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats.

    PubMed

    Leri, Francesco; Burns, Lindsay H

    2005-10-01

    Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague-Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg/kg/infusion), but not slightly higher doses (10 and 100 pg/kg/infusion), enhanced oxycodone (0.1 mg/kg/infusion) intravenous self-administration, suggesting a reduced rewarding potency per infusion. During tests of reinstatement performed in extinction conditions, co-self-administration of any of these three NTX doses significantly reduced drug-seeking precipitated by priming injections of oxycodone (0.25 mg/kg, s.c.), a drug-conditioned cue, or foot-shock stress. During self-administration on a progressive-ratio schedule, animals self-administering oxycodone (0.1 mg/kg/infusion)+NTX (1 pg/kg/infusion) reached a "break-point" sooner and showed a trend toward less responding compared to rats self-administering oxycodone alone (0.1 mg/kg/infusion). In the final experiment, the addition of ultra-low-dose NTX (10 pg/kg, s.c.) enhanced the acute stimulatory effect of oxycodone (1 mg/kg, s.c.), as well as locomotor sensitization produced by repeated oxycodone administration (7 x 1 mg/kg, s.c.). In summary, this work shows that ultra-low-dose NTX co-treatment augments the locomotor effects of oxycodone as it enhances opioid analgesia, but reduces oxycodone's rewarding potency and subsequent vulnerability to relapse.

  9. Low-dose photons modify liver response to simulated solar particle event protons.

    PubMed

    Gridley, Daila S; Coutrakon, George B; Rizvi, Asma; Bayeta, Erben J M; Luo-Owen, Xian; Makinde, Adeola Y; Baqai, Farnaz; Koss, Peter; Slater, James M; Pecaut, Michael J

    2008-03-01

    The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons ((57)Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event.

  10. Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia.

    PubMed

    Boyapati, Ann; Sinclair, Rodney

    2013-02-01

    We report on a 47-year-old man who was initially treated with finasteride for androgenetic alopecia. Despite continuous treatment, after year 4 his hair density was not as good as at year 2, and low-dose dutasteride at 0.5 mg/week was added to the finasteride therapy. This resulted in a dramatic increase in his hair density, demonstrating that combined therapy with finasteride and dutasteride can improve hair density in patients already taking finasteride. PMID:22686691

  11. Resource Letter EIRLD-1: Effects of ionizing radiation at low doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    1999-05-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books, and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer and noncancer outcomes), effects of dose rate, relationship to background, supra linearity and homesis, and policy implications.

  12. Noise Reduction in Low-Dose X-Ray Fluoroscopy for Image-Guided Radiation Therapy

    SciTech Connect

    Wang Jing Zhu Lei; Xing Lei

    2009-06-01

    Purpose: To improve the quality of low-dose X-ray fluoroscopic images using statistics-based restoration algorithm so that the patient fluoroscopy can be performed with reduced radiation dose. Method and Materials: Noise in the low-dose fluoroscopy was suppressed by temporal and spatial filtering. The temporal correlation among neighboring frames was considered by the Karhunen-Loeve (KL) transform (i.e., principal component analysis). After the KL transform, the selected neighboring frames of fluoroscopy were decomposed to uncorrelated and ordered principal components. For each KL component, a penalized weighted least-squares (PWLS) objective function was constructed to restore the ideal image. The penalty was chosen as anisotropic quadratic, and the penalty parameter in each KL component was inversely proportional to its corresponding eigenvalue. Smaller KL eigenvalue is associated with the KL component of lower signal-to-noise ratio (SNR), and a larger penalty parameter should be used for such KL component. The low-dose fluoroscopic images were acquired using a Varian Acuity simulator. A quality assurance phantom and an anthropomorphic chest phantom were used to evaluate the presented algorithm. Results: In the images restored by the proposed KL domain PWLS algorithm, noise is greatly suppressed, whereas fine structures are well preserved. Average improvement rate of SNR is 75% among selected regions of interest. Comparison studies with traditional techniques, such as the mean and median filters, show that the proposed algorithm is advantageous in terms of structure preservation. Conclusions: The proposed noise reduction algorithm can significantly improve the quality of low-dose X-ray fluoroscopic image and allows for dose reduction in X-ray fluoroscopy.

  13. Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

    PubMed

    Chandler, Joshua D; Wongtrakool, Cherry; Banton, Sophia A; Li, Shuzhao; Orr, Michael L; Barr, Dana Boyd; Neujahr, David C; Sutliff, Roy L; Go, Young-Mi; Jones, Dean P

    2016-07-01

    Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half-life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd-treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low-dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low-dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low-dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma.

  14. Low-dose photons modify liver response to simulated solar particle event protons.

    PubMed

    Gridley, Daila S; Coutrakon, George B; Rizvi, Asma; Bayeta, Erben J M; Luo-Owen, Xian; Makinde, Adeola Y; Baqai, Farnaz; Koss, Peter; Slater, James M; Pecaut, Michael J

    2008-03-01

    The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons ((57)Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event. PMID:18302490

  15. Resource Letter EIRLD-2: Effects of Ionizing Radiation at Low Doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    2012-04-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer, and non-cancer outcomes), effects of dose rate, relationship to background, supra linearity and hormesis, and policy implications.

  16. Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

    PubMed

    Chandler, Joshua D; Wongtrakool, Cherry; Banton, Sophia A; Li, Shuzhao; Orr, Michael L; Barr, Dana Boyd; Neujahr, David C; Sutliff, Roy L; Go, Young-Mi; Jones, Dean P

    2016-07-01

    Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half-life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd-treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low-dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low-dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low-dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma. PMID:27401458

  17. Low-dose effects of bisphenol A on mammary gland development in rats.

    PubMed

    Mandrup, K; Boberg, J; Isling, L K; Christiansen, S; Hass, U

    2016-07-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected. PMID:27088260

  18. Radiation-induced apoptosis in SCID Mousespleen after a low-dose irration

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.

    Purpose: To estimate the effects of space radiation on health of space crews, we aimed to clarify whether pre-irradiation at a low-dose interferes in a p53-centered signal transduction pathway induced by radiation. By using a severe combined immunodeficiency (Scid) mouse defective DNA-PK activity, we examined the role of DNA-PK activity in radioadaptation induced by low-dose irradiation. Methodology: Specific pathogen free 5-week-old fe male mice of Scid and the parental mice (CB-17 Icr+/+) were irradiated with X-rays at 3.0 Gy 1, 2, 3 or 4 weeks after conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after irradiation. Bax on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method using HISTOFINE SAB-PO(R) kit (Nichirei Co., Tokyo, Japan). Apoptosis incidence in the sections was measured by staining with HE staining. Results: The frequency of Bax- and apoptosis -positive cells increased up to 12 h after irradiation at 3.0 Gy in the spleen of CB-17 Icr+/+ and Scid mice. However, they were not observed by irradiation with low dose at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before challenging acute irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by irradiation at 3.0 Gy was depressed in the spleen of CB-17 Icr+/+ mice, but not Scid mice. Conclusions: These data suggest that DNA-PKcs (expressed in CB-17 Icr+/+, not Scid mice) might play a major role on radioadaptation induced by pre-irradiation at low dose in mice spleen. We expect that the present findings will provide useful information for the care of space crews' health.

  19. Data Integration Reveals Key Homeostatic Mechanisms Following Low Dose Radiation Exposure

    SciTech Connect

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-01

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time - with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24 – 72 hr). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress were measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 were experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation.

  20. Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low Dose Aspirin

    PubMed Central

    Dudley, Alicia; Thomason, John; Fritz, Sara; Grady, Jesse; Stokes, John; Wills, Robert; Pinchuk, Lesya; Mackin, Andrew; Lunsford, Kari

    2014-01-01

    Background Low dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are non-responsive to the anti-platelet effects of aspirin (‘aspirin resistance’). Hypothesis/Objectives That low dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression. Animals Twenty-four healthy dogs Methods A repeated measures study. Platelet function (PFA-100® closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B2 (11-dTXB2) was evaluated prior to and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, non-responders, and inconsistent responders. Results Low dose aspirin increased closure times significantly (62% by Day 10, P<0.001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, −29.7%–136.1%) (P=0.047) and 72% on Day 10 (range, −0.37–210.36%) (P<0.001). Platelet COX-2 MFI increased significantly by 34% (range, −29.2–270.4%) on Day 3 (P = 0.003) and 74% (range, −19.7–226.2%) on Day 10 (P<0.001). Urinary 11-dTXB2 concentrations significantly (P=0.005, P<0.001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production. Conclusions and Clinical Importance Low dose aspirin consistently inhibits platelet function in approximately one third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. Pre-treatment COX isoform expression did not predict aspirin resistance. PMID:23278865

  1. Complications of Anterior Cervical Fusion using a Low-dose Recombinant Human Bone Morphogenetic Protein-2

    PubMed Central

    Kukreja, Sunil; Ahmed, Osama I; Haydel, Justin; Nanda, Anil

    2015-01-01

    Objective There are several reports, which documented a high incidence of complications following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior cervical fusions (ACFs). The objective of this study is to share our experience with low-dose rhBMP-2 in anterior cervical spine. Methods We performed a retrospective analysis of 197 patients who underwent anterior cervical fusion (ACF) with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) during 2007-2012. A low-dose rhBMP-2 (0.7mg/level) sponge was placed exclusively within the cage. In 102 patients demineralized bone matrix (DBM) was filled around the BMP sponge. Incidence and severity of dysphagia was determined by 5 points SWAL-QOL scale. Results Two patients had prolonged hospitalization due to BMP unrelated causes. Following the discharge, 13.2%(n=26) patients developed dysphagia and 8.6%(n=17) patients complained of neck swelling. More than half of the patients (52.9%, n=9) with neck swelling also had associated dysphagia; however, only 2 of these patients necessitated readmission. Both of these patients responded well to the intravenous dexamethasone. The use of DBM did not affect the incidence and severity of complications (p>0.05). Clinico-radiological evidence of fusion was not observed in 2 patients. Conclusion A low-dose rhBMP-2 in ACFs is not without risk. However, the incidence and severity of complications seem to be lower with low-dose BMP placed exclusively inside the cage. Packing DBM putty around the BMP sponge does not affect the safety profile of rhBMP-2 in ACFs. PMID:26217385

  2. The biobehavioral and neuroimmune impact of low-dose ionizing radiation

    PubMed Central

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2011-01-01

    In the clinical setting, repeated exposures (10–30) to low-doses of ionizing radiation (≤ 200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 h and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477

  3. Inconsistencies and open questions regarding low-dose health effects of ionizing radiation.

    PubMed Central

    Nussbaum, R H; Köhnlein, W

    1994-01-01

    The effects on human health of exposures to ionizing radiation at low doses have long been the subject of dispute. In this paper we focus on open questions regarding the health effects of low-dose exposures that require further investigations. Seemingly contradictory findings of radiation health effects have been reported for the same exposed populations, or inconsistent estimates of radiation risks were found when different populations and exposure conditions were compared. Such discrepancies may be indicative of differences in sensitivities among the applied methods of epidemiological analysis or indicative of significant discrepancies in health consequences after comparable total exposures of different populations under varying conditions. We focus first on inconsistencies and contradictions in presentations of the state of knowledge by different authoritative experts. We then review studies that found positive associations between exposure and risks in dose ranges where traditional notions (generalized primarily from high-dose studies of A-bomb survivors or exposed animals) would have predicted negligible effects. One persistent notion in many reviews of low-dose effects is the hypothesis of reduced biological effectiveness of fractionated low-dose exposures, compared to that of the same acute dose. This assumption is not supported by data on human populations. From studies of populations that live in contaminated areas, more and more evidence is accumulating on unusual rates of various diseases other than radiation-induced malignancies, health effects that are suspected to be associated with relatively low levels of internal exposures originating from radioactive fallout. Such effects include congenital defects, neonatal mortality, stillbirths, and possibly genetically transmitted disease. A range of open questions challenges scientists to test imaginative hypotheses about induction of disease by radiation with novel research strategies. Images Figure 1. PMID

  4. Low-dose effects of bisphenol A on mammary gland development in rats.

    PubMed

    Mandrup, K; Boberg, J; Isling, L K; Christiansen, S; Hass, U

    2016-07-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected.

  5. The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

    PubMed

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2012-02-01

    In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice.

  6. Low-dose ionising radiation and cardiovascular diseases--Strategies for molecular epidemiological studies in Europe.

    PubMed

    Kreuzer, Michaela; Auvinen, Anssi; Cardis, Elisabeth; Hall, Janet; Jourdain, Jean-Rene; Laurier, Dominique; Little, Mark P; Peters, Annette; Raj, Ken; Russell, Nicola S; Tapio, Soile; Zhang, Wei; Gomolka, Maria

    2015-01-01

    It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5-5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases. PMID:26041268

  7. Low-dose IL-2 selectively activates subsets of CD4+ Tregs and NK cells

    PubMed Central

    Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye; Koreth, John; Kim, Haesook T.; Paul, Nicole E.; Murase, Kazuyuki; Whangbo, Jennifer; Alho, Ana C.; Nikiforow, Sarah; Cutler, Corey; Ho, Vincent T.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.; Blazar, Bruce R.; Lacerda, Joao F.; Soiffer, Robert J.

    2016-01-01

    CD4+ regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood. Using mass cytometry, we demonstrate that low concentrations of IL-2 selectively induce STAT5 phosphorylation in Helios+ CD4Tregs and CD56brightCD16– NK cells in vitro. Preferential activation and expansion of Helios+ CD4Tregs and CD56brightCD16– NK cells was also demonstrated in patients with chronic GVHD receiving low-dose IL-2. With prolonged IL-2 treatment for 48 weeks, phenotypic changes were also observed in Helios– CD4Tregs. The effects of low-dose IL-2 therapy on conventional CD4+ T cells and CD8+ T cells were limited to increased expression of PD-1 on effector memory T cells. These studies reveal the selective effects of low-dose IL-2 therapy on Helios+ CD4Tregs and CD56bright NK cells that constitutively express high-affinity IL-2 receptors as well as the indirect effects of prolonged exposure to low concentrations of IL-2 in vivo. PMID:27812545

  8. Low-Dose Isotretinoin: An Option for Difficult-to-Treat Papulopustular Rosacea.

    PubMed

    van Zuuren, Esther J; Fedorowicz, Zbys

    2016-06-01

    Rosacea is a chronic disease with a profound impact on quality of life. Although there are a range of treatments for its many manifestations, some cases are difficult to treat. Sbidian et al. show in this double-blind, randomized, placebo-controlled trial that low-dose isotretinoin can be effective in treating difficult-to-treat and frequently relapsing papulopustular rosacea. PMID:27212646

  9. Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

    PubMed Central

    2011-01-01

    Introduction Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus. Case presentation We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion) with the insulin analogue lispro (Humalog®) in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg) p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI) despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog®. Conclusion Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog®), triggered by an unknown endogenous mechanism. PMID:22145998

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

    PubMed

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

    2013-01-01

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

  11. Low-Dose Aronia melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity

    PubMed Central

    Case, A. J.; Agraz, D.; Ahmad, I. M.; Zimmerman, M. C.

    2016-01-01

    Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity. PMID:26770655

  12. Perinatal exposure to low-dose methoxychlor impairs testicular development in C57BL/6 mice.

    PubMed

    Du, Xiaohong; Zhang, Hua; Liu, Yuanwu; Yu, Wanpeng; Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.

  13. Sheet resistance monitoring of low dose implants using the double implant technique

    NASA Astrophysics Data System (ADS)

    Smith, A. K.; Johnson, W. H.; Keenan, W. A.; Rigik, Michael; Kleppinger, Rob

    Sheet resistance has become an industry standard for monitoring high and medium dose ion implants. For low dose there are two sheet resistance techniques available, the direct implant technique and the double implant technique. Careful processing has extended the range of direct sheet resistance measurements down to doses of 2E11 ions/cm 2. The double implant technique requires an initial implant to create an easily measured sheet resistance layer that serves as the test vehicle for the second implant. The dose of the second implant is measured by monitoring the change in the sheet resistance due to the implant damage created by the second implant into the first. This double implant technique is not limited to low dose nor to species that are electrically active in the substrate. The sensitivity of any measurement is defined as the percent change in the measured value divided by the percent change with monitored value. The direct sheet resistance technique has a sensitivity of about unity in the low dose region. For the double implant technique, however, the sensitivity can be increased up to 1.5 by varying the initial dose. The sensitivity of the double implant technique can thus be tailored to the particular dose to be monitored. Several double implant experiments will be reviewed to demonstrate the range, repeatability, accuracy, resolution and sensitivity of the technique.

  14. An optimized colony forming assay for low-dose-radiation cell survival measurement

    SciTech Connect

    Zhu J.; Sutherland B.; Hu W.; Ding N.; Ye C.; Usikalu M.; Li S.; Hu B.; Zhou G.

    2011-11-01

    The aim of this study is to develop a simple and reliable method to quantify the cell survival of low-dose irradiations. Two crucial factors were considered, the same number of cells plated in each flask and an appropriate interval between cell plating and irradiation. For the former, we optimized cell harvest with trypsin, diluted cells in one container, and directly seeded cells on the bottom of flasks in a low density before irradiation. Reproducible plating efficiency was obtained. For the latter, we plated cells on the bottom of flasks and then monitored the processing of attachment, cell cycle variations, and the plating efficiency after exposure to 20 cGy of X-rays. The results showed that a period of 4.5 h to 7.5 h after plating was suitable for further treatment. In order to confirm the reliability and feasibility of our method, we also measured the survival curves of these M059K and M059J glioma cell lines by following the optimized protocol and obtained consistent results reported by others with cell sorting system. In conclusion, we successfully developed a reliable and simple way to measure the survival fractions of human cells exposed to low dose irradiation, which might be helpful for the studies on low-dose radiation biology.

  15. Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

    PubMed

    Kalyonova, L F; Novikova, M A; Kostolomova, E G

    2015-01-01

    The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis. PMID:25567196

  16. [Low dose estrogens and synthetic estrogens. Options for hormone replacement therapy in climacteric women].

    PubMed

    Velasco-Murillo, Vitelio

    2007-01-01

    A significant increase for cardiovascular disease and breast cancer risks was found in the Women's Health Initiative study in 2002, for current users of conjugated equine estrogens in the habitual dose of 0.625 mg for hormone replacement therapy (HRT) for treating menopausal symptoms. This unexpected finding has caused new-found interest in the world to determine if the use of low-dose estrogens or synthetic estrogens can be useful and safer. At present, there is no scientific evidence about the reduction of such risks with the use of low-dose estrogens. Current medical information has showed that HRT is effective to treat climacteric syndrome and to prevent postmenopausal osteoporosis. In addition, HRT reduces significantly the frequency and severity of vaginal bleeding. Currently the Climacteric and Menopause Program at the Instituto Mexicano del Seguro Social only considers the use of conjugated equine estrogens at the standard dose (0.625 mg). The purpose of this paper is to present some results about use of low-dose estrogens and points of view about synthetic estrogens found in current medical literature. This review aims at contributing to the analysis a possible future use of this type of hormone treatment within the institutional program with the goal of giving safer options to clinicians in managing women with menopausal symptoms.

  17. Low-Dose Aronia melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity.

    PubMed

    Case, A J; Agraz, D; Ahmad, I M; Zimmerman, M C

    2016-01-01

    Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity.

  18. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  19. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension

    PubMed Central

    Schmeisser, Sebastian; Schmeisser, Kathrin; Weimer, Sandra; Groth, Marco; Priebe, Steffen; Fazius, Eugen; Kuhlow, Doreen; Pick, Denis; Einax, Jürgen W; Guthke, Reinhard; Platzer, Matthias; Zarse, Kim; Ristow, Michael

    2013-01-01

    Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. This requires two transcription factors, namely DAF-16 and SKN-1, which employ the metallothionein MTL-2 as well as the mitochondrial transporter TIN-9.1 to extend lifespan. Taken together, low-dose arsenite extends lifespan, providing evidence for nonlinear dose-response characteristics of toxin-mediated stress resistance and longevity in a multicellular organism. PMID:23534459

  20. Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

    PubMed Central

    Vaiserman, Alexander M.

    2010-01-01

    Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

  1. Adaption By Low Dose Radiation Exposure: A Look at Scope and Limitations for Radioprotection.

    PubMed

    Mitchel, Ron E J

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to "as low as reasonably achievable" (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations.

  2. [The effect of extremely low doses of the novel regulatory plant proteins ].

    PubMed

    Krasnov, M S; Margasiuk, D V; Iamskov, I A; Iamskova, V P

    2003-01-01

    Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially. PMID:12881977

  3. Radiation-Induced Bystander Effects: Evidence for an Adaptive Response to Low Dose Exposures?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2006-01-01

    This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response appears to require a quorum in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. While a death response might appear to be adverse, the position is argued in this paper that it is in fact protective and removes damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation, so called “background damage”, it is possible that low doses exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “U-shaped” dose response curves. In this scenario, the level of “adaptive” or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors. PMID:18648593

  4. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient.

    PubMed

    Kim, Jin Ok; Jun, Dae Won; Tae, Hye Jin; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul; Hahm, Joon Soo

    2015-03-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC. PMID:25834806

  5. Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival.

    PubMed

    Woo, Su Jung; Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; In Yong, Ji; Ryu, Eun Ji; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Park, Sungyeon; Im, Seung Kwon; Kim, Duk-Soo; Kwon, Oh-Shin; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-11-15

    Oxidative stress is considered a major factor in various neuronal diseases including ischemia-reperfusion injury. Proviral Integration Moloney 2 (PIM2) proteins, one of the families of PIM kinases, play crucial roles in cell survival. However, the functions of PIM2 protein against ischemia are not understood. Therefore, the protective effects of PIM2 against oxidative stress-induced hippocampal HT22 cell death and brain ischemic injury were evaluated using Tat-PIM2, a cell permeable fusion protein. Tat-PIM2 protein transduced into hippocampal HT22 cells. Low doses of transduced Tat-PIM2 protein protected against oxidative stress-induced cell death including DNA damage and markedly inhibited the activation of mitogen activated protein kinase (MAPKs), NF-κB and the expression levels of Bax protein. Furthermore, Tat-PIM2 protein transduced into the CA1 region of the hippocampus and significantly prevented neuronal cell death in an ischemic insult animal model. These results indicated that low doses of Tat-PIM2 protein protects against oxidative stress-induced neuronal cell death, suggesting low doses of Tat-PIM2 protein provides a potential therapeutic agent against oxidative stress-induced neuronal diseases including ischemia. PMID:26365288

  6. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process

    PubMed Central

    Alessio, Nicola; Del Gaudio, Stefania; Capasso, Stefania; Di Bernardo, Giovanni; Cappabianca, Salvatore; Cipollaro, Marilena; Peluso, Gianfranco; Galderisi, Umberto

    2015-01-01

    Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites. We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis. The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence. An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination). PMID:25544750

  7. Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2.

    PubMed

    Dwyer, Connor J; Ward, Natasha C; Pugliese, Alberto; Malek, Thomas R

    2016-06-01

    Dysregulation of the immune system contributes to the breakdown of immune regulation, leading to autoimmune diseases, such as type 1 diabetes (T1D). Current therapies for T1D include daily insulin, due to pancreatic β-cell destruction to maintain blood glucose levels, suppressive immunotherapy to decrease the symptoms associated with autoimmunity, and islet transplantation. Genetic risks for T1D have been linked to IL-2 and IL-2R signaling pathways that lead to the breakdown of self-tolerance mechanisms, primarily through altered regulatory T cell (Treg) function and homeostasis. In attempt to correct such deficits, therapeutic administration of IL-2 at low doses has gained attention due to the capacity to boost Tregs without the unwanted stimulation of effector T cells. Preclinical and clinical studies utilizing low-dose IL-2 have shown promising results to expand Tregs due to their high selective sensitivity to respond to IL-2. These results suggest that low-dose IL-2 therapy represents a new class of immunotherapy for T1D by promoting immune regulation rather than broadly suppressing unwanted and beneficial immune responses. PMID:27076179

  8. Low Doses of Celecoxib Attenuate Gut Barrier Failure During Experimental Peritonitis

    PubMed Central

    Short, Scott S.; Wang, Jin; Castle, Shannon L.; Fernandez, G. Esteban; Smiley, Nancy; Zobel, Michael; Pontarelli, Elizabeth M.; Papillon, Stephanie C.; Grishin, Anatoly V.; Ford, Henri R.

    2013-01-01

    The intestinal barrier becomes compromised during systemic inflammation, leading to entry of luminal bacteria into the host and gut origin sepsis. Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study we examined the role of cyclooxygenase-2 (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut barrier failure during experimental peritonitis in mice. I.p. injection of LPS or cecal ligation and puncture (CLP) increased the levels of COX-2 and its product prostaglandin E2 (PGE2) in the ileal mucosa, caused pathologic sloughing of the intestinal epithelium, increased passage of FITC-dextran and bacterial translocation across the barrier, and increased internalization of the tight junction-associated proteins JAM-A and ZO-1. Luminal instillation of PGE2 in an isolated ileal loop increased transepithelial passage of FITC-dextran. Low doses (0.5–1 mg/kg), but not a higher dose (5 mg/kg) of the specific COX-2 inhibitor Celecoxib partially ameliorated the inflammatory gut barrier failure. These results demonstrate that high levels of COX-2-derived PGE2 seen in the mucosa during peritonitis contribute to gut barrier failure, presumably by compromising tight junctions. Low doses of specific COX-2 inhibitors may blunt this effect while preserving the homeostatic function of COX-2-derived prostanoids. Low doses of COX-2 inhibitors may find use as an adjunct barrier-protecting therapy in critically ill patients. PMID:24126890

  9. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  10. Single-neuron axonal pathfinding under geometric guidance: low-dose-methylmercury developmental neurotoxicity test.

    PubMed

    Wei, Lina; Sweeney, Andrew J; Sheng, Liyuan; Fang, Yu; Kindy, Mark S; Xi, Tingfei; Gao, Bruce Z

    2014-09-21

    Because the nervous system is most vulnerable to toxicants during development, there is a crucial need for a highly sensitive developmental-neurotoxicity-test model to detect potential toxicants at low doses. We developed a lab-on-chip wherein single-neuron axonal pathfinding under geometric guidance was created using soft lithography and laser cell-micropatterning techniques. After coating the surface with L1, an axon-specific member of the Ig family of cell adhesion molecules (CAMs), and optimizing microunit geometric parameters, we introduced low-dose methylmercury, a well-known, environmentally significant neurotoxicant, in the shared medium. Its developmental neurotoxicity was evaluated using a novel axonal pathfinding assay including axonal turning and branching rates at turning points in this model. Compared to the conventional neurite-outgrowth assay, this model's detection threshold for low-dose methylmercury was 10-fold more sensitive at comparable exposure durations. These preliminary results support study of developmental effects of known and potential neurotoxicants on axon pathfinding. This novel assay model would be useful to study neuronal disease mechanisms at the single-cell level. To our knowledge, the potential of methylmercury chloride to cause acute in vitro developmental neurotoxicity (DNT) at such a low dosage has not been reported. This is the first DNT test model with high reproducibility to use single-neuron axonal pathfinding under precise geometric guidance. PMID:25041816

  11. [The effect of extremely low doses of the novel regulatory plant proteins ].

    PubMed

    Krasnov, M S; Margasiuk, D V; Iamskov, I A; Iamskova, V P

    2003-01-01

    Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially.

  12. TH-A-18C-03: Noise Correlation in CBCT Projection Data and Its Application for Noise Reduction in Low-Dose CBCT

    SciTech Connect

    ZHANG, H; Huang, J; Ma, J; Chen, W; Ouyang, L; Wang, J

    2014-06-15

    Purpose: To study the noise correlation properties of cone-beam CT (CBCT) projection data and to incorporate the noise correlation information to a statistics-based projection restoration algorithm for noise reduction in low-dose CBCT. Methods: In this study, we systematically investigated the noise correlation properties among detector bins of CBCT projection data by analyzing repeated projection measurements. The measurements were performed on a TrueBeam on-board CBCT imaging system with a 4030CB flat panel detector. An anthropomorphic male pelvis phantom was used to acquire 500 repeated projection data at six different dose levels from 0.1 mAs to 1.6 mAs per projection at three fixed angles. To minimize the influence of the lag effect, lag correction was performed on the consecutively acquired projection data. The noise correlation coefficient between detector bin pairs was calculated from the corrected projection data. The noise correlation among CBCT projection data was then incorporated into the covariance matrix of the penalized weighted least-squares (PWLS) criterion for noise reduction of low-dose CBCT. Results: The analyses of the repeated measurements show that noise correlation coefficients are non-zero between the nearest neighboring bins of CBCT projection data. The average noise correlation coefficients for the first- and second- order neighbors are about 0.20 and 0.06, respectively. The noise correlation coefficients are independent of the dose level. Reconstruction of the pelvis phantom shows that the PWLS criterion with consideration of noise correlation (PWLS-Cor) results in a lower noise level as compared to the PWLS criterion without considering the noise correlation (PWLS-Dia) at the matched resolution. Conclusion: Noise is correlated among nearest neighboring detector bins of CBCT projection data. An accurate noise model of CBCT projection data can improve the performance of the statistics-based projection restoration algorithm for low-dose

  13. Gel microdrop flow cytometry assay for low-dose studies of chemical and radiation cytotoxicity.

    PubMed

    Bogen, K T; Enns, L; Hall, L C; Keating, G A; Weinfeld, M; Murphy, G; Wu, R W; Panteleakos, F N

    2001-03-01

    Low-level cytotoxicity may affect low-dose dose-response relations for cancer and other endpoints. Conventional colony-forming assays are rarely sensitive enough to examine small changes in cell survival and growth. Automated image-analysis techniques are limited to ca. 10(4) cells/plate. An alternative method involves encapsulation of single proliferating cells into ca. 35-75-microm-diameter agarose gel microdrops (GMDs) that are randomly grouped, differential exposure of these groups, culture at 37 degrees C for 3-5 days, and finally GMD analysis by flow cytometry (FC) to determine the ratio of GMDs containing multiple versus single cells as a measure of clonogenic survival. This GMD/FC assay was used to examine low-dose cell killing induced by a cooked-meat mutagen/rodent-carcinogen (MeIQx) in DNA-repair-deficient/metabolically-sensitive CHO cells. Results of conventional colony-forming assays using up to 30 replicate plates indicate a shouldered, threshold-like dose-response; in contrast, those obtained using the GMD/FC assay suggest "hypersensitivity"-like nonlinearity in dose-response. The GMD/FC assay was also applied to human A549 lung cells after GMD-encapsulation and gamma radiation followed by culture for a total of 4 days, to examine survival after exposure to > or =100 cGy delivered at a relatively low dose rate (0.18 cGy/min). Dose-response for clonogenic growth was again observed to be reduced with apparent nonlinear suggesting hypersensitivity between 0 and 50 cGy, insofar as doses of 5 and 10 cGy appear to be ca. fivefold more effective per unit dose than the 50- or 100-cGy doses used. The GMD/FC assay may thus reveal low-dose dose-response relations for chemical and radiation effects on cell proliferation/killing with implications for low-dose risk assessment.

  14. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    SciTech Connect

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  15. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  16. European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

    PubMed

    Landolfi, R; Marchioli, R

    1997-01-01

    Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is

  17. A Low-Dose Ipsilateral Lung Restriction Improves 3-D Conformal Planning for Partial Breast Radiation Therapy

    SciTech Connect

    Mitchell, Tracy; Truong, Pauline T.; Salter, Lee; Graham, Cathy; Gaffney, Helene; Beckham, Wayne; Olivotto, Ivo A.

    2011-04-01

    In trials of 3D conformal external beam partial breast radiotherapy (PBRT), the dosimetrist must balance the priorities of achieving high conformity to the target versus minimizing low-dose exposure to the normal structures. This study highlights the caveat that in the absence of a low-dose lung restriction, the use of relatively en-face fields may meet trial-defined requirements but expose the ipsilateral lung to unnecessary low-dose radiation. Adding a low-dose restriction that {<=}20% of the ipsilateral lung should receive 10% of the prescribed dose resulted in successful plans in 88% of cases. This low-dose lung limit should be used in PBRT planning.

  18. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    SciTech Connect

    Gridley, Daila S.

    2008-10-31

    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

  19. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow.

    PubMed

    Pacilè, S; Brun, F; Dullin, C; Nesterest, Y I; Dreossi, D; Mohammadi, S; Tonutti, M; Stacul, F; Lockie, D; Zanconati, F; Accardo, A; Tromba, G; Gureyev, T E

    2015-08-01

    Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography.

  20. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow.

    PubMed

    Pacilè, S; Brun, F; Dullin, C; Nesterest, Y I; Dreossi, D; Mohammadi, S; Tonutti, M; Stacul, F; Lockie, D; Zanconati, F; Accardo, A; Tromba, G; Gureyev, T E

    2015-08-01

    Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography. PMID:26309770

  1. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow

    PubMed Central

    Pacilè, S.; Brun, F.; Dullin, C.; Nesterest, Y. I.; Dreossi, D.; Mohammadi, S.; Tonutti, M.; Stacul, F.; Lockie, D.; Zanconati, F.; Accardo, A.; Tromba, G.; Gureyev, T. E.

    2015-01-01

    Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography. PMID:26309770

  2. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low