Correlation of ultra-low dose chest CT findings with physiologic measures of asbestosis.

PubMed

Manners, David; Wong, Patrick; Murray, Conor; Teh, Joelin; Kwok, Yi Jin; de Klerk, Nick; Alfonso, Helman; Franklin, Peter; Reid, Alison; Musk, A W Bill; Brims, Fraser J H

2017-08-01

The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis. • Interobserver agreement for the ILD score using prone ULDCT is good. • Prone ULDCT appearances of ILD correlate with changes in spirometric observations. • Prone ULDCT appearances of ILD correlate strongly with changes in gas transfer. • Prone ULDCT may provide sufficient radiological evidence to inform the diagnosis of asbestosis.

Convolutional auto-encoder for image denoising of ultra-low-dose CT.

PubMed

Nishio, Mizuho; Nagashima, Chihiro; Hirabayashi, Saori; Ohnishi, Akinori; Sasaki, Kaori; Sagawa, Tomoyuki; Hamada, Masayuki; Yamashita, Tatsuo

2017-08-01

The purpose of this study was to validate a patch-based image denoising method for ultra-low-dose CT images. Neural network with convolutional auto-encoder and pairs of standard-dose CT and ultra-low-dose CT image patches were used for image denoising. The performance of the proposed method was measured by using a chest phantom. Standard-dose and ultra-low-dose CT images of the chest phantom were acquired. The tube currents for standard-dose and ultra-low-dose CT were 300 and 10 mA, respectively. Ultra-low-dose CT images were denoised with our proposed method using neural network, large-scale nonlocal mean, and block-matching and 3D filtering. Five radiologists and three technologists assessed the denoised ultra-low-dose CT images visually and recorded their subjective impressions of streak artifacts, noise other than streak artifacts, visualization of pulmonary vessels, and overall image quality. For the streak artifacts, noise other than streak artifacts, and visualization of pulmonary vessels, the results of our proposed method were statistically better than those of block-matching and 3D filtering (p-values < 0.05). On the other hand, the difference in the overall image quality between our proposed method and block-matching and 3D filtering was not statistically significant (p-value = 0.07272). The p-values obtained between our proposed method and large-scale nonlocal mean were all less than 0.05. Neural network with convolutional auto-encoder could be trained using pairs of standard-dose and ultra-low-dose CT image patches. According to the visual assessment by radiologists and technologists, the performance of our proposed method was superior to that of large-scale nonlocal mean and block-matching and 3D filtering.

Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

PubMed

Imai, Rumi; Miyazaki, Osamu; Horiuchi, Tetsuya; Asano, Keisuke; Nishimura, Gen; Sago, Haruhiko; Nosaka, Shunsuke

2017-06-01

Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes) -0.5 , the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

PubMed

Paquette, Jay; Olmstead, Mary C; Olmstead, Mary

2005-12-01

Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.

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 levels simulated, sparse view protocols with 41 and 24 views best balanced the tradeoff between electronic noise and aliasing artifacts. In terms of lesion activity error and ensemble RMSE of the PET images, these two protocols, when combined with MBIR, are able to provide results that are comparable to the baseline full dose CT scan. View interpolation significantly improves the performance of FDK reconstruction but was not necessary for MBIR. With the more technically feasible continuous exposure data acquisition, the CT images show an increase in azimuthal blur compared to tube pulsing. However, this blurring generally does not have a measureable impact on PET reconstructed images. Our simulations demonstrated that ultra-low-dose CT-based attenuation correction can be achieved at dose levels on the order of 0.044 mAs with little impact on PET image quality. Highly sparse 41- or 24- view ultra-low dose CT scans are feasible for PET attenuation correction, providing the best tradeoff between electronic noise and view aliasing artifacts. The continuous exposure acquisition mode could potentially be implemented in current commercially available scanners, thus enabling sparse view data acquisition without requiring x-ray tubes capable of operating in a pulsing mode.

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

PubMed Central

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

2015-01-01

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. Methods 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 seconds. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.04375 mAs, were investigated. Both the analytical 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. Results 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 simulated, sparse view protocols with 41 and 24 views best balanced the tradeoff between electronic noise and aliasing artifacts. In terms of lesion activity error and ensemble RMSE of the PET images, these two protocols, when combined with MBIR, are able to provide results that are comparable to the baseline full dose CT scan. View interpolation significantly improves the performance of FDK reconstruction but was not necessary for MBIR. With the more technically feasible continuous exposure data acquisition, the CT images show an increase in azimuthal blur compared to tube pulsing. However, this blurring generally does not have a measureable impact on PET reconstructed images. Conclusions Our simulations demonstrated that ultra-low-dose CT-based attenuation correction can be achieved at dose levels on the order of 0.044 mAs with little impact on PET image quality. Highly sparse 41- or 24- view ultra-low dose CT scans are feasible for PET attenuation correction, providing the best tradeoff between electronic noise and view aliasing artifacts. The continuous exposure acquisition mode could potentially be implemented in current commercially available scanners, thus enabling sparse view data acquisition without requiring x-ray tubes capable of operating in a pulsing mode. PMID:26352168

Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics

DTIC Science & Technology

2008-05-01

in non-human primates. a. Study behavioral effects of ultra- low doses of intrathecal N/OFQ over a wide dose range using a warm water tail...threshold of monkeys. Figure 1 compares the effects of ultra- low doses of intrathecal N/OFQ (i.e., 1 fmol and 1 pmol) with those of a mu opioid...findings indicate that ultra- low doses of intrathecal N/OFQ did not change the monkey’s thermal nociceptive threshold (Figure 1, middle panels

Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

PubMed Central

Rakwal, Randeep; Agrawal, Ganesh Kumar; Shibato, Junko; Imanaka, Tetsuji; Fukutani, Satoshi; Tamogami, Shigeru; Endo, Satoru; Sahoo, Sarata Kumar; Masuo, Yoshinori; Kimura, Shinzo

2009-01-01

We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (γ) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s. PMID:19399245

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kirby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley;

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

PubMed

Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

2010-04-16

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Metabolomic analysis for the protective effects of mangiferin on sepsis-induced lung injury in mice.

PubMed

Wang, Yilin; Liu, Yang; Cao, Qiqi; Shi, Xuan; Lu, Hongtao; Gao, Songyan; Yang, Rui

2018-06-01

This study aimed to investigate the efficacy of mangiferin, including its known antioxidant and anti-inflammatory effects on sepsis-induced lung injury induced by a classical cecal ligation and puncture (CLP) models in mouse using a metabolomics approach. A total of 24 mice were randomly divided into four groups: the sham group was given saline before sham operation. The CLP group received the CLP operation only. HMF and LMF groups were given mangiferin treatment of high dose and low dose of mangiferin, respectively, before the CLP operation. One week after treatment, the mice were sacrificed and their lungs were collected for metabolomics analysis. We developed ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to perform lung metabolic profiling analysis. With the methods of principal component analysis and partial least squares discriminant analysis, 58 potential metabolites associated with amino acid metabolism, purine metabolism, lipid metabolism and energy regulation were observed to be increased or reduced in HMF and LMF groups compared with the CLP group. Conclusively, our results suggest that mangiferin plays a protective role in the moderation of sepsis-induced lung injury through reducing oxidative stress, regulating lipid metabolism and energy biosynthesis. Copyright © 2018 John Wiley & Sons, Ltd.

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Reduced lung-cancer mortality with low-dose computed tomographic screening.

PubMed

Aberle, Denise R; Adams, Amanda M; Berg, Christine D; Black, William C; Clapp, Jonathan D; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine; Marcus, Pamela M; Sicks, JoRean D

2011-08-04

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

2008-10-01

Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated μ-Opioid Receptor–Gs Coupling

PubMed Central

Largent-Milnes, Tally M.; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H.; Vanderah, Todd W.

2017-01-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in μ-opioid receptor (MOR)–G protein coupling from Gi/o to Gs that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L5/L6 spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to Gs in the damaged (ipsilateral) spinal dorsal horn. This MOR-Gs coupling occurred without changing Gi/o coupling levels and without changing the expression of MOR or Gα proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-Gs coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-Gs coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this Gs coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-Gs coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. PMID:18468954

Low doses of cyclic AMP-phosphodiesterase inhibitors rapidly evoke opioid receptor-mediated thermal hyperalgesia in naïve mice which is converted to prominent analgesia by cotreatment with ultra-low-dose naltrexone.

PubMed

Crain, Stanley M; Shen, Ke-Fei

2008-09-22

Systemic (s.c.) injection in naïve mice of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors, e.g. 3-isobutyl-1-methylxanthine [(IBMX) or caffeine, 10 mg/kg] or the more specific cAMP-PDE inhibitor, rolipram (1 mug/kg), rapidly evokes thermal hyperalgesia (lasting >5 h). These effects appear to be mediated by enhanced excitatory opioid receptor signaling, as occurs during withdrawal in opioid-dependent mice. Cotreatment of these mice with ultra-low-dose naltrexone (NTX, 0.1 ng/kg-1 pg/kg, s.c.) results in prominent opioid analgesia (lasting >4 h) even when the dose of rolipram is reduced to 1 pg/kg. Cotreatment of these cAMP-PDE inhibitors in naïve mice with an ultra-low-dose (0.1 ng/kg) of the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) or the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA) also results in opioid analgesia. These excitatory effects of cAMP-PDE inhibitors in naïve mice may be mediated by enhanced release of small amounts of endogenous bimodally-acting (excitatory/inhibitory) opioid agonists by neurons in nociceptive networks. Ultra-low-dose NTX, nor-BNI or beta-FNA selectively antagonizes high-efficacy excitatory (hyperalgesic) Gs-coupled opioid receptor-mediated signaling in naïve mice and results in rapid conversion to inhibitory (analgesic) Gi/Go-coupled opioid receptor-mediated signaling which normally requires activation by much higher doses of opioid agonists. Cotreatment with a low subanalgesic dose of kelatorphan, an inhibitor of multiple endogenous opioid peptide-degrading enzymes, stabilizes endogenous opioid agonists released by cAMP-PDE inhibitors, resulting in conversion of the hyperalgesia to analgesia without requiring selective blockade of excitatory opioid receptor signaling. The present study provides a novel pharmacologic paradigm that may facilitate development of valuable non-narcotic clinical analgesics utilizing cotreatment with ultra-low-dose rolipram plus ultra-low-dose NTX or related agents.

Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

PubMed

Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

2017-05-01

Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.

PubMed

Tompkins, David Andrew; Lanier, Ryan K; Harrison, Joseph A; Strain, Eric C; Bigelow, George E

2010-07-01

Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed. Preclinical and clinical studies have shown that opioids combined with ultra-low-dose naltrexone (NTX) may have increased analgesic potency and have suggested reduced abuse or dependence liability. This study addressed whether addition of ultra-low-dose naltrexone might decrease the abuse liability of oxycodone (OXY) in humans. This double-blind, placebo-controlled study systematically examined the subjective and physiological effects of combining oral OXY and ultra-low NTX doses in 14 experienced opioid abusers. Seven acute drug conditions given at least 5 days apart were compared in a within-subject crossover design: placebo, OXY 20 mg, OXY 40 mg, plus each of the active OXY doses combined with 0.0001 and 0.001 mg NTX. The methods were sensitive to detecting opioid effects on abuse liability indices, with significant differences between all OXY conditions and placebo as well as between 20 and 40 mg OXY doses on positive subjective ratings (e.g., "I feel a good drug effect" or "I like the drug"), on observer- and participant-rated opioid agonist effects, and on a drug-versus-money value rating. There were no significant differences or evident trends associated with the addition of either NTX dose on any abuse liability indices. The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.

Oxycodone plus ultra-low-dose naltrexone attenuates neuropathic pain and associated mu-opioid receptor-Gs coupling.

PubMed

Largent-Milnes, Tally M; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H; Vanderah, Todd W

2008-08-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in mu-opioid receptor (MOR)-G protein coupling from G(i/o) to G(s) that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L(5)/L(6) spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to G(s) in the damaged (ipsilateral) spinal dorsal horn. This MOR-G(s) coupling occurred without changing G(i/o) coupling levels and without changing the expression of MOR or Galpha proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-G(s) coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-G(s) coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this G(s) coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-G(s) coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. The current study investigates whether Oxytrex (oxycodone with an ultra-low dose of naltrexone) alleviates mechanical and thermal hypersensitivities in an animal model of neuropathic pain over a period of 7 days, given locally or systemically. In this report, we first describe an injury-induced shift in mu-opioid receptor coupling from G(i/o) to G(s), suggesting why a mu-opioid agonist may have reduced efficacy in the nerve-injured state. These data present a novel approach to neuropathic pain therapy.

Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

PubMed

Roshanpour, Maryam; Ghasemi, Mehdi; Riazi, Kiarash; Rafiei-Tabatabaei, Neda; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza

2009-02-01

The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

Preoperative assessment of pleural adhesion by Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) with Adaptive Iterative Dose Reduction using Three-Dimensional processing (AIDR-3D).

PubMed

Hashimoto, Masayuki; Nagatani, Yukihiro; Oshio, Yasuhiko; Nitta, Norihisa; Yamashiro, Tsuneo; Tsukagoshi, Shinsuke; Ushio, Noritoshi; Mayumi, Masayuki; Kimoto, Tatsuya; Igarashi, Tomoyuki; Yoshigoe, Makoto; Iwai, Kyohei; Tanaka, Koki; Sato, Shigetaka; Sonoda, Akinaga; Otani, Hideji; Murata, Kiyoshi; Hanaoka, Jun

2018-01-01

To assess the feasibility of Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) for distinguishing pleural aspects with localized pleural adhesion (LPA) from those without. Twenty-seven patients underwent 4D-ULDCT during a single respiration with a 16cm-coverage of the body axis. The presence and severity of LPA was confirmed by their intraoperative thoracoscopic findings. A point on the pleura and a corresponding point on the outer edge of the costal bone were placed in identical axial planes at end-inspiration. The distance of the two points (PCD), traced by automatic tracking functions respectively, was calculated at each respiratory phase. The maximal and average change amounts in PCD (PCD MCA and PCD ACA ) were compared among 110 measurement points (MPs) without LPA, 16MPs with mild LPA and 10MPs with severe LPA in upper lung field cranial to the bronchial bifurcation (ULF), and 150MPs without LPA, 17MPs with mild LPA and 9MPs with severe LPA in lower lung field caudal to the bronchial bifurcation (LLF) using the Mann-Whitney U test. In the LLF, PCD ACA as well as PCD MCA demonstrated a significant difference among non-LPA, mild LPA and severe LPA (18.1±9.2, 12.3±6.2 and 5.0±3.3mm) (p<0.05). Also in the ULF, PCD ACA showed a significant difference among three conditions (9.2±5.5, 5.7±2.8 and 2.2±0.4mm, respectively) (p<0.05), whereas PCD MCA for mild LPA was similar to that for non-LPA (12.3±5.9 and 17.5±11.0mm). Four D-ULDCT could be a useful non-invasive preoperative assessment modality for the detection of the presence or severity of LPA. Copyright © 2017 Elsevier B.V. All rights reserved.

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

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

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Ultra low dose CT screen-detected non-malignant incidental findings in the Western Australian Asbestos Review Programme.

PubMed

Murray, Conor P; Wong, Patrick M; Teh, Joelin; de Klerk, Nick; Rosenow, Tim; Alfonso, Helman; Reid, Alison; Franklin, Peter; Musk, A W Bill; Brims, Fraser J H

2016-11-01

Computed tomography (CT)-based studies of asbestos-exposed individuals report a high prevalence of lung cancer, but the utility of low dose CT (LDCT) to screen asbestos-exposed populations is not established. We aimed to describe the prevalence of indeterminate pulmonary nodules and incidental findings on chest LDCT of asbestos-exposed subjects in Western Australia. A total of 906 subjects from the Western Australian Asbestos Review Programme underwent LDCT of the chest as part of regular annual review. An indeterminate (solid) nodule was defined as >50 mm 3 and part-solid/non-solid nodules >5 mm. The presence of asbestos-related diseases was recorded with a standardized report. Subjects were mostly (81%) men with a median age of 70 years. Fifty-eight (6.5%) participants were current smokers, 511 (56.4%) ex-smokers and 325 (36.4%) never-smokers. One hundred and four indeterminate nodules were detected in 77 subjects (8.5%); of these, eight cases had confirmed lung cancer (0.88%). Eighty-seven subjects (9.6%) had incidental findings that required further investigation, 42 (4.6%) from lower airways inflammation. The majority of nodules were solid, 4-6 mm and more common with age. Five hundred and eighty (64%) subjects had pleural plaques, and 364 (40.2%) had evidence of interstitial lung disease. The prevalence of LDCT-detected indeterminate lung nodules in 906 individuals with significant asbestos exposure was 8.5%, lower than many other CT studies. Clinically important incidental findings were found in 9.4%, predominantly related to lower respiratory tract inflammation. LDCT appears to effectively describe asbestos-related diseases and is likely to be an acceptable modality to monitor asbestos-exposed individuals. © 2016 Asian Pacific Society of Respirology.

Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?

PubMed

Farahmand, Shervin; Ahmadi, Omid; Dehpour, Ahmadreza; Khashayar, Patricia

2012-01-01

The present study aims to assess the influence of ultra-low doses of opioid antagonists on the analgesic properties of opioids and their side effects. In the present randomized, double-blind controlled trial, the influence of the combination of ultra-low-dose naltrexone and morphine on the total opioid requirement and the frequency of the subsequent side effects was compared with that of morphine alone (added with placebo) in patients with trauma in the upper or lower extremities. Although the morphine and naltrexone group required 0.04 mg more opioids during the study period, there was no significant difference between the opioid requirements of the 2 groups. Nausea was less frequently reported in patients receiving morphine and naltrexone. The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea. Copyright © 2012 Elsevier Inc. All rights reserved.

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;

Ultra-high spatial resolution multi-energy CT using photon counting detector technology

NASA Astrophysics Data System (ADS)

Leng, S.; Gutjahr, R.; Ferrero, A.; Kappler, S.; Henning, A.; Halaweish, A.; Zhou, W.; Montoya, J.; McCollough, C.

2017-03-01

Two ultra-high-resolution (UHR) imaging modes, each with two energy thresholds, were implemented on a research, whole-body photon-counting-detector (PCD) CT scanner, referred to as sharp and UHR, respectively. The UHR mode has a pixel size of 0.25 mm at iso-center for both energy thresholds, with a collimation of 32 × 0.25 mm. The sharp mode has a 0.25 mm pixel for the low-energy threshold and 0.5 mm for the high-energy threshold, with a collimation of 48 × 0.25 mm. Kidney stones with mixed mineral composition and lung nodules with different shapes were scanned using both modes, and with the standard imaging mode, referred to as macro mode (0.5 mm pixel and 32 × 0.5 mm collimation). Evaluation and comparison of the three modes focused on the ability to accurately delineate anatomic structures using the high-spatial resolution capability and the ability to quantify stone composition using the multi-energy capability. The low-energy threshold images of the sharp and UHR modes showed better shape and texture information due to the achieved higher spatial resolution, although noise was also higher. No noticeable benefit was shown in multi-energy analysis using UHR compared to standard resolution (macro mode) when standard doses were used. This was due to excessive noise in the higher resolution images. However, UHR scans at higher dose showed improvement in multi-energy analysis over macro mode with regular dose. To fully take advantage of the higher spatial resolution in multi-energy analysis, either increased radiation dose, or application of noise reduction techniques, is needed.

The National Lung Screening Trial (NLST) | Division of Cancer Prevention

Cancer.gov

The National Lung Screening Trial (NLST) compared two ways of detecting lung cancer: low-dose helical computed tomography (CT) and standard chest X-ray. Both chest X-rays and low-dose helical CT scans have been used to find lung cancer early, but the effects of these screening techniques on lung cancer mortality rates had not been determined. NLST enrolled 53,454 current or

Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

PubMed

Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

2016-07-01

The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Incidental renal tumours on low-dose CT lung cancer screening exams.

PubMed

Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

2017-06-01

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

Projected Clinical, Resource Use, and Fiscal Impacts of Implementing Low-Dose Computed Tomography Lung Cancer Screening in Medicare.

PubMed

Roth, Joshua A; Sullivan, Sean D; Goulart, Bernardo H L; Ravelo, Arliene; Sanderson, Joanna C; Ramsey, Scott D

2015-07-01

The Centers for Medicare and Medicaid Services (CMS) recently issued a national coverage determination that provides reimbursement for low-dose computed tomography (CT) lung cancer screening for enrollees age 55 to 77 years with ≥ 30-pack-year smoking history who currently smoke or quit in the last 15 years. The clinical, resource use, and fiscal impacts of this change in screening coverage policy remain uncertain. We developed a simulation model to forecast the 5-year health outcome impacts of the CMS low-dose CT screening policy in Medicare compared with no screening. The model used data from the National Lung Screening Trial, CMS enrollment statistics and reimbursement schedules, and peer-reviewed literature. Outcomes included counts of screening examinations, patient cases of lung cancer detected, stage distribution, and total and per-enrollee per-month fiscal impact. Over 5 years, we project that low-dose CT screening will result in 10.7 million more low-dose CT scans, 52,000 more lung cancers detected, and increased overall expenditure of $6.8 billion ($2.22 per Medicare enrollee per month). The most fiscally impactful factors were the average cost-per-screening episode, proportion of enrollees eligible for screening, and cost of treating stage I lung cancer. Low-dose CT screening is expected to increase lung cancer diagnoses, shift stage at diagnosis toward earlier stages, and substantially increase Medicare expenditures over a 5-year time horizon. These projections can inform planning efforts by Medicare administrators, contracted health care providers, and other stakeholders. Copyright © 2015 by American Society of Clinical Oncology.

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.

PubMed

Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

2011-03-01

Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

A photon recycling approach to the denoising of ultra-low dose X-ray sequences.

PubMed

Hariharan, Sai Gokul; Strobel, Norbert; Kaethner, Christian; Kowarschik, Markus; Demirci, Stefanie; Albarqouni, Shadi; Fahrig, Rebecca; Navab, Nassir

2018-06-01

Clinical procedures that make use of fluoroscopy may expose patients as well as the clinical staff (throughout their career) to non-negligible doses of radiation. The potential consequences of such exposures fall under two categories, namely stochastic (mostly cancer) and deterministic risks (skin injury). According to the "as low as reasonably achievable" principle, the radiation dose can be lowered only if the necessary image quality can be maintained. Our work improves upon the existing patch-based denoising algorithms by utilizing a more sophisticated noise model to exploit non-local self-similarity better and this in turn improves the performance of low-rank approximation. The novelty of the proposed approach lies in its properly designed and parameterized noise model and the elimination of initial estimates. This reduces the computational cost significantly. The algorithm has been evaluated on 500 clinical images (7 patients, 20 sequences, 3 clinical sites), taken at ultra-low dose levels, i.e. 50% of the standard low dose level, during electrophysiology procedures. An average improvement in the contrast-to-noise ratio (CNR) by a factor of around 3.5 has been found. This is associated with an image quality achieved at around 12 (square of 3.5) times the ultra-low dose level. Qualitative evaluation by X-ray image quality experts suggests that the method produces denoised images that comply with the required image quality criteria. The results are consistent with the number of patches used, and they demonstrate that it is possible to use motion estimation techniques and "recycle" photons from previous frames to improve the image quality of the current frame. Our results are comparable in terms of CNR to Video Block Matching 3D-a state-of-the-art denoising method. But qualitative analysis by experts confirms that the denoised ultra-low dose X-ray images obtained using our method are more realistic with respect to appearance.

Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury.

PubMed

Liu, Yung-Yang; Chiang, Chi-Huei; Hung, Shih-Chieh; Chian, Chih-Feng; Tsai, Chen-Liang; Chen, Wei-Chih; Zhang, Haibo

2017-01-01

Hypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs). However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R) lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels. I/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells) and high (1×106 cells) dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined. I/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS), pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism. Hypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis.

Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury

PubMed Central

Chiang, Chi-Huei; Hung, Shih-Chieh; Chian, Chih-Feng; Tsai, Chen-Liang; Chen, Wei-Chih; Zhang, Haibo

2017-01-01

Background Hypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs). However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R) lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels. Methods I/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells) and high (1×106 cells) dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined. Results I/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS), pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism. Conclusions Hypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis. PMID:29117205

Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

PubMed

Stang, Andreas; Schuler, Martin; Kowall, Bernd; Darwiche, Kaid; Kühl, Hilmar; Jöckel, Karl-Heinz

2015-09-18

It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany. The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany. If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening. The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation.

PubMed

Webster, Lynn R

2007-08-01

Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

PubMed Central

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

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

Fisher, Darrell R.; Weller, Richard E.

From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10more » females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 cGy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.« less

Adduction of DNA with MTBE and TBA in mice studied by accelerator mass spectrometry.

PubMed

Yuan, Y; Wang, H F; Sun, H F; Du, H F; Xu, L H; Liu, Y F; Ding, X F; Fu, D P; Liu, K X

2007-12-01

Methyl tert-butyl ether (MTBE) is a currently worldwide used octane enhancer substituting for lead alkyls and gasoline oxygenate. Our previous study using doubly (14)C-labeled MTBE [(CH(3))(3) (14)CO(14)CH(3)] has shown that MTBE binds DNA to form DNA adducts at low dose levels in mice. To elucidate the mechanism of the binding reaction, in this study, the DNA adducts with singly (14)C-labeled MTBE, which was synthesized from (14)C-methanol and tert-butyl alcohol (TBA), or (14)C-labeled TBA in mice have been measured by ultra sensitive accelerator mass spectrometry. The results show that the methyl group of MTBE and tert-butyl alcohol definitely form adducts with DNA in mouse liver, lung, and kidney. The methyl group of MTBE is the predominant binding part in liver, while the methyl group and the tert-butyl group give comparable contributions to the adduct formation in lung and kidney.

Results of initial low-dose computed tomographic screening for lung cancer.

PubMed

Church, Timothy R; Black, William C; Aberle, Denise R; Berg, Christine D; Clingan, Kathy L; Duan, Fenghai; Fagerstrom, Richard M; Gareen, Ilana F; Gierada, David S; Jones, Gordon C; Mahon, Irene; Marcus, Pamela M; Sicks, JoRean D; Jain, Amanda; Baum, Sarah

2013-05-23

Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs. At 33 U.S. centers, from August 2002 through April 2004, we enrolled asymptomatic participants, 55 to 74 years of age, with a history of at least 30 pack-years of smoking. The participants were randomly assigned to undergo annual screening, with the use of either low-dose CT or chest radiography, for 3 years. Nodules or other suspicious findings were classified as positive results. This article reports findings from the initial screening examination. A total of 53,439 eligible participants were randomly assigned to a study group (26,715 to low-dose CT and 26,724 to chest radiography); 26,309 participants (98.5%) and 26,035 (97.4%), respectively, underwent screening. A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the radiography group had a positive screening result; in the respective groups, 6369 participants (90.4%) and 2176 (92.7%) had at least one follow-up diagnostic procedure, including imaging in 5717 (81.1%) and 2010 (85.6%) and surgery in 297 (4.2%) and 121 (5.2%). Lung cancer was diagnosed in 292 participants (1.1%) in the low-dose CT group versus 190 (0.7%) in the radiography group (stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112). Sensitivity and specificity were 93.8% and 73.4% for low-dose CT and 73.5% and 91.3% for chest radiography, respectively. The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Inhaled uranium ore dust and lung cancer risk in rats.

PubMed

Mitchel, R E; Jackson, J S; Heinmiller, B

1999-02-01

Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h d(-1), 5 days per week for 65 weeks to one of two concentrations of natural uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant radon content. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime. Lung uranium burdens, measured at the time of death of each animal, declined exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. Lymph node specific burdens ranged from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed groups, respectively. There was no difference in tumor latency between the groups. Absorbed dose to the lung was calculated for each animal in the study. The average doses for all the animals exposed to the low and high dust aerosol concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both groups. The frequency of primary lung tumors was also calculated as a function of dose increment for both exposed groups individually and combined. The data indicate that, in spite of the above result, lung tumor frequency was not directly proportional to dose. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting dose rate may be a more important determinant of lung cancer risk than dose. Conversely, non-malignant lung tumors were significantly correlated with low lung burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation and that malignant tumor risk was not directly proportional to dose, but was directly proportional to dose rate.

Synthesis and dose interval dependent hepatotoxicity evaluation of intravenously administered polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticle on Wistar rats.

PubMed

Rajan, Balan; Sathish, Shanmugam; Balakumar, Subramanian; Devaki, Thiruvengadam

2015-03-01

Superparamagnetic iron oxide nanoparticles are being used in medical imaging, drug delivery, cancer therapy, and so on. However, there is a direct need to identify any nanotoxicity associated with these nanoparticles. However uncommon, drug-induced liver injury (DILI) is a major health concern that challenges pharmaceutical industry and drug regulatory agencies alike. In this study we have synthesized and evaluated the dose interval dependent hepatotoxicity of polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticles (PUSPIOs). To assess the hepatotoxicity of intravenously injected PUSPIOs, alterations in basic clinical parameters, hematological parameters, hemolysis assay, serum levels of liver marker enzymes, serum and liver lipid peroxidation (LPO) levels, enzymatic antioxidant levels, and finally histology of liver, kidney, spleen, lung, brain, and heart tissues were studied in control and experimental Wistar rat groups over a 30-day period. The results of our study showed a significant increase in the aspartate transaminase (AST) enzyme activity at a dose of 10mg/kg b.w. PUSPIOs twice a week. Besides, alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) enzyme activity showed a slender increase when compared with control experimental groups. A significant increase in the serum and liver LPO levels at a dose of 10mg/kg b.w. PUSPIOs twice a week was also observed. Histological analyses of liver, kidney, spleen, lung, brain and heart tissue samples showed no obvious uncharacteristic changes. In conclusion, PUSPIOs were found to posses excellent biocompatibility and Wistar rats showed much better drug tolerance to the dose of 10mg/kg b.w. per week than the dose of 10mg/kg b.w. twice a week for the period of 30 days. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 19489 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... announced below concerns Low Dose CT Lung Cancer Screening: Informed Decision Making and Smoking Cessation... include the initial review, discussion, and evaluation of ``Low Dose CT Lung Cancer Screening: Informed...

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

NASA Astrophysics Data System (ADS)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

PubMed

Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

2016-02-01

Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. Copyright © 2016 Chenery et al.

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.

2015-09-01

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

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

Husain, Mainul, E-mail: mainul.husain@hc-sc.gc.ca; Saber, Anne T., E-mail: ats@nrcwe.dk; Guo, Charles, E-mail: charles.guo@hc-sc.gc.ca

2013-06-15

We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO{sub 2}). Female C57BL/6 mice were exposed to rutile nano-TiO{sub 2} via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO{sub 2} in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO{sub 2} in the lungs upmore » to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p < 0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO{sub 2} in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO{sub 2} were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose group.« less

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

DTIC Science & Technology

2013-08-31

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...slice of a series, total lung volume, total lung tissue mass and frequency distribution of lung CT numbers expressed in Hounsfield Units (HU) were...tomography; HU: Hounsfield units ; CTDIvol: volumetric computed tomography dose index; DLP: dose length product; E: effective dose; SD: standard deviation

Recovery from manual metal arc-stainless steel welding-fume exposure induced lung fibrosis in Sprague-Dawley rats.

PubMed

Yu, Il Je; Song, Kyung Seuk; Chang, Hee Kyung; Han, Jeong Hee; Chung, Yong Hyun; Han, Kuy Tae; Chung, Kyu Hyuck; Chung, Ho Keun

2003-08-28

Welders with radiographic pneumoconiosis abnormalities have exhibited a gradual clearing of the X-ray identified effects following removal from exposure. In some cases, the pulmonary fibrosis associated with welding fumes appears in a more severe form in welders. Accordingly, to investigate the disease and recovery process of pneumoconiosis induced by welding-fume exposure, rats were exposed to welding fumes with concentrations of 63.6+/-4.1 mg/m(3) (low dose) and 107.1+/-6.3 mg/m(3) (high dose) of total suspended particulate for 2 h per day in an inhalation chamber for a total of 2 h or 15, 30, 60 or 90 days. Thereafter, the rats were no longer exposed and allowed to recover from the welding fume-induced lung fibrosis for 90 days. When compared to the unexposed control group, the lung weights significantly increased in both the low- and high-dose rats from day 15 to 90. A histopathological examination combined with fibrosis-specific staining revealed that the lungs from the low-dose rats did not exhibit any significant progressive fibrotic changes. Whereas, the lungs from the high-dose rats exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Recovery, evaluated based on the body and lung weights and a histopathological examination, was observed in both the high and low-dose rats that were exposed up to 30 days. The rats exposed for 60-90 days at the low dose also recovered from the fibrosis, yet the rats exposed for 60-90 days at the high dose did not fully recover. Consequently, recovery from pneumoconiosis induced by welding-fume exposure was observed when the degree of exposure was short-term and moderate.

A feasibility study on the use of phantoms with statistical lung masses for determining the uncertainty in the dose absorbed by the lung from broad beams of incident photons and neutrons

PubMed Central

Khankook, Atiyeh Ebrahimi; Hakimabad, Hashem Miri

2017-01-01

Abstract Computational models of the human body have gradually become crucial in the evaluation of doses absorbed by organs. However, individuals may differ considerably in terms of organ size and shape. In this study, the authors sought to determine the energy-dependent standard deviations due to lung size of the dose absorbed by the lung during external photon and neutron beam exposures. One hundred lungs with different masses were prepared and located in an adult male International Commission on Radiological Protection (ICRP) reference phantom. Calculations were performed using the Monte Carlo N-particle code version 5 (MCNP5). Variation in the lung mass caused great uncertainty: ~90% for low-energy broad parallel photon beams. However, for high-energy photons, the lung-absorbed dose dependency on the anatomical variation was reduced to <1%. In addition, the results obtained indicated that the discrepancy in the lung-absorbed dose varied from 0.6% to 8% for neutron beam exposure. Consequently, the relationship between absorbed dose and organ volume was found to be significant for low-energy photon sources, whereas for higher energy photon sources the organ-absorbed dose was independent of the organ volume. In the case of neutron beam exposure, the maximum discrepancy (of 8%) occurred in the energy range between 0.1 and 5 MeV. PMID:28077627

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

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

2016-05-01

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. 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. 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-related mortality (185·82 [95% CI 162·17-211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial. Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis.

PubMed

Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

2015-11-01

The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5-30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5-30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose-volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P < 0.05). Multivariate analysis indicated AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102-0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm(3); sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm(3) than with AVS5 < 564.9 cm(3) (P = 0.008). Low-dose irradiation relative volumes and MLD of the bilateral or ipsilateral lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A BMI-adjusted ultra-low-dose CT angiography protocol for the peripheral arteries-Image quality, diagnostic accuracy and radiation exposure.

PubMed

Schreiner, Markus M; Platzgummer, Hannes; Unterhumer, Sylvia; Weber, Michael; Mistelbauer, Gabriel; Loewe, Christian; Schernthaner, Ruediger E

2017-08-01

To investigate radiation exposure, objective image quality, and the diagnostic accuracy of a BMI-adjusted ultra-low-dose CT angiography (CTA) protocol for the assessment of peripheral arterial disease (PAD), with digital subtraction angiography (DSA) as the standard of reference. In this prospective, IRB-approved study, 40 PAD patients (30 male, mean age 72 years) underwent CTA on a dual-source CT scanner at 80kV tube voltage. The reference amplitude for tube current modulation was personalized based on the body mass index (BMI) with 120 mAs for [BMI≤25] or 150 mAs for [2570%) was assessed by two readers independently and compared to subsequent DSA. Radiation exposure was assessed with the computed tomography dose index (CTDIvol) and the dosis-length product (DLP). Objective image quality was assessed via contrast- and signal-to-noise ratio (CNR and SNR) measurements. Radiation exposure and image quality were compared between the BMI groups and between the BMI-adjusted ultra-low-dose protocol and the low-dose institutional standard protocol (ISP). The BMI-adjusted ultra-low-dose protocol reached high diagnostic accuracy values of 94% for Reader 1 and 93% for Reader 2. Moreover, in comparison to the ISP, it showed significantly (p<0.001) lower CTDIvol (1.97±0.55mGy vs. 4.18±0.62 mGy) and DLP (256±81mGy x cm vs. 544±83mGy x cm) but similar image quality (p=0.37 for CNR). Furthermore, image quality was similar between BMI groups (p=0.86 for CNR). A CT protocol that incorporates low kV settings with a personalized (BMI-adjusted) reference amplitude for tube current modulation and iterative reconstruction enables very low radiation exposure CTA, while maintaining good image quality and high diagnostic accuracy in the assessment of PAD. Copyright © 2017 Elsevier B.V. All rights reserved.

WE-D-207-01: Background and Clinical Implementation of a Screening Program

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

Aberle, D.

2015-06-15

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

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

NONE

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

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

Xu, H; Cape Breton Cancer Centre, Sydney, NS

Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o±10o and 140o±10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio ofmore » V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.« less

Commentary on Inhaled 239PuO 2 in Dogs — A Prophylaxis against Lung Cancer?

DOE PAGES

Cuttler, Jerry M.; Feinendegen, Ludwig E.

2015-01-01

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO 2 inhalation, as a prophylaxis against lung cancer.

Commentary on Inhaled 239PuO 2 in Dogs — A Prophylaxis against Lung Cancer?

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

Cuttler, Jerry M.; Feinendegen, Ludwig E.

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO 2 inhalation, as a prophylaxis against lung cancer.

Can sinogram-affirmed iterative (SAFIRE) reconstruction improve imaging quality on low-dose lung CT screening compared with traditional filtered back projection (FBP) reconstruction?

PubMed

Yang, Wen Jie; Yan, Fu Hua; Liu, Bo; Pang, Li Fang; Hou, Liang; Zhang, Huan; Pan, Zi Lai; Chen, Ke Min

2013-01-01

To evaluate the performance of sinogram-affirmed iterative (SAFIRE) reconstruction on image quality of low-dose lung computed tomographic (CT) screening compared with filtered back projection (FBP). Three hundred four patients for annual low-dose lung CT screening were examined by a dual-source CT system at 120 kilovolt (peak) with reference tube current of 40 mA·s. Six image serials were reconstructed, including one data set of FBP and 5 data sets of SAFIRE with different reconstruction strengths from 1 to 5. Image noise was recorded; and subjective scores of image noise, images artifacts, and the overall image quality were also assessed by 2 radiologists. The mean ± SD weight for all patients was 66.3 ± 12.8 kg, and the body mass index was 23.4 ± 3.2. The mean ± SD dose-length product was 95.2 ± 30.6 mGy cm, and the mean ± SD effective dose was 1.6 ± 0.5 mSv. The observation agreements for image noise grade, artifact grade, and the overall image quality were 0.785, 0.595 and 0.512, respectively. Among the overall 6 data sets, both the measured mean objective image noise and the subjective image noise of FBP was the highest, and the image noise decreased with the increasing of SAFIRE reconstruction strength. The data sets of S3 obtained the best image quality scores. Sinogram-affirmed iterative reconstruction can significantly improve image quality of low-dose lung CT screening compared with FBP, and SAFIRE with reconstruction strength 3 was a pertinent choice for low-dose lung CT.

Natural Killer Cell Recruitment to the Lung During Influenza A Virus Infection Is Dependent on CXCR3, CCR5, and Virus Exposure Dose

PubMed Central

Carlin, Lindsey E.; Hemann, Emily A.; Zacharias, Zeb R.; Heusel, Jonathan W.; Legge, Kevin L.

2018-01-01

Natural killer (NK) cells are vital components of the antiviral immune response, but their contributions in defense against influenza A virus (IAV) are not well understood. To better understand NK cell responses during IAV infections, we examined the magnitude, kinetics, and contribution of NK cells to immunity and protection during high- and low-dose IAV infections. Herein, we demonstrate an increased accumulation of NK cells in the lung in high-dose vs. low-dose infections. In part, this increase is due to the local proliferation of pulmonary NK cells. However, the majority of NK cell accumulation within the lungs and airways during an IAV infection is due to recruitment that is partially dependent upon CXCR3 and CCR5, respectively. Therefore, altogether, our results demonstrate that NK cells are actively recruited to the lungs and airways during IAV infection and that the magnitude of the recruitment may relate to the inflammatory environment found within the tissues during high- and low-dose IAV infections. PMID:29719539

Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

2016-03-01

Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

Lung Cancer Screening with Low-Dose Computed Tomography for Primary Care Providers

PubMed Central

Richards, Thomas B.; White, Mary C.; Caraballo, Ralph S.

2015-01-01

This review provides an update on lung cancer screening with low-dose computed tomography (LDCT) and its implications for primary care providers. One of the unique features of lung cancer screening is the potential complexity in patient management if an LDCT scan reveals a small pulmonary nodule. Additional tests, consultation with multiple specialists, and follow-up evaluations may be needed to evaluate whether lung cancer is present. Primary care providers should know the resources available in their communities for lung cancer screening with LDCT and smoking cessation, and the key points to be addressed in informed and shared decision-making discussions with patients. PMID:24830610

The possible protective role of pumpkin seed oil in an animal model of acid aspiration pneumonia: Light and electron microscopic study.

PubMed

Omar, Nesreen Moustafa; Sarhan, Nahla Reda

2017-03-01

Aspiration pneumonitis is a common problem occurring in many clinical disorders. Pumpkin seed oil (PO) is a rich source of antioxidants. This work aimed to assess the effect of PO on the lung histopathological changes induced by acid aspiration. Forty male albino rats assigned to four groups were used. Rats of control group were instilled intratracheally with normal saline 2mL/kg. HCL group instilled with 2mL/kg of HCL 0.1N, pH 1.25. PO group received pumpkin seed oil (PO) orally (∼1375mg/kgbw/day) for 7days. HCL+PO group instilled with 2mL/kg of HCL 0.1N, pH 1.25 and received PO at the same dose of PO group. Lung tissue samples were processed for light, electron microscopic and immunohistochemical study using anti inducible NO synthase (iNOS). The lung of HCL group demonstrated thickened interalveolar septa, inflammatory cell infiltration and significant increase in the area percent of collagenous fibers and immune expression of iNOS. Ultra structurally, disrupted alveolocapillay membrane, degenerated type II pneumocytes and plentiful alveolar macrophages were evident. PO administration partially attenuated these histological and ultra structural alterations and reduced iNOS immune-expression in lung tissue. In conclusion, PO has a protective effect against HCL aspiration lung injury most probably through its antioxidant activity. Copyright © 2017 Elsevier GmbH. All rights reserved.

A conserved post-transcriptional BMP2 switch in lung cells.

PubMed

Jiang, Shan; Fritz, David T; Rogers, Melissa B

2010-05-15

An ultra-conserved sequence in the bone morphogenetic protein 2 (BMP2) 3' untranslated region (UTR) markedly represses BMP2 expression in non-transformed lung cells. In contrast, the ultra-conserved sequence stimulates BMP2 expression in transformed lung cells. The ultra-conserved sequence functions as a post-transcriptional cis-regulatory switch. A common single-nucleotide polymorphism (SNP, rs15705, +A1123C), which has been shown to influence human morphology, disrupts a conserved element within the ultra-conserved sequence and altered reporter gene activity in non-transformed lung cells. This polymorphism changed the affinity of the BMP2 RNA for several proteins including nucleolin, which has an increased affinity for the C allele. Elevated BMP2 synthesis is associated with increased malignancy in mouse models of lung cancer and poor lung cancer patient prognosis. Understanding the cis- and trans-regulatory factors that control BMP2 synthesis is relevant to the initiation or progression of pathologies associated with abnormal BMP2 levels. (c) 2010 Wiley-Liss, Inc.

SU-C-206-07: A Practical Sparse View Ultra-Low Dose CT Acquisition Scheme for PET Attenuation Correction in the Extended Scan Field-Of-View

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

Miao, J; Fan, J; Gopinatha Pillai, A

Purpose: To further reduce CT dose, a practical sparse-view acquisition scheme is proposed to provide the same attenuation estimation as higher dose for PET imaging in the extended scan field-of-view. Methods: CT scans are often used for PET attenuation correction and can be acquired at very low CT radiation dose. Low dose techniques often employ low tube voltage/current accompanied with a smooth filter before backprojection to reduce CT image noise. These techniques can introduce bias in the conversion from HU to attenuation values, especially in the extended CT scan field-of-view (FOV). In this work, we propose an ultra-low dose CTmore » technique for PET attenuation correction based on sparse-view acquisition. That is, instead of an acquisition of full amount of views, only a fraction of views are acquired. We tested this technique on a 64-slice GE CT scanner using multiple phantoms. CT scan FOV truncation completion was performed based on the published water-cylinder extrapolation algorithm. A number of continuous views per rotation: 984 (full), 246, 123, 82 and 62 have been tested, corresponding to a CT dose reduction of none, 4x, 8x, 12x and 16x. We also simulated sparse-view acquisition by skipping views from the fully-acquired view data. Results: FBP reconstruction with Q. AC filter on reduced views in the full extended scan field-of-view possesses similar image quality to the reconstruction on acquired full view data. The results showed a further potential for dose reduction compared to the full acquisition, without sacrificing any significant attenuation support to the PET. Conclusion: With the proposed sparse-view method, one can potential achieve at least 2x more CT dose reduction compared to the current Ultra-Low Dose (ULD) PET/CT protocol. A pre-scan based dose modulation scheme can be combined with the above sparse-view approaches, which can even further reduce the CT scan dose during a PET/CT exam.« less

Radiation exposure and lung disease in today's nuclear world.

PubMed

Deas, Steven D; Huprikar, Nikhil; Skabelund, Andrew

2017-03-01

Ionizing radiation poses important health risks. The per capita annual dose rate has increased in the United States and there is increasing concern for the risks posed by low-dose occupational exposure among workers in nuclear industries and healthcare. Recent nuclear accidents and concern for terrorism have heightened concern for catastrophic, high-dose ionizing radiation exposure. This review will highlight recent research into the risks to lung health posed by ionizing radiation exposure and into potential treatments. Angiotensin-converting enzyme inhibitors and some antioxidants have shown promise as mitigators, to decrease pneumonitis and fibrosis when given after exposure. Studies of survivors of nuclear catastrophes have shown increased risk for lung cancer, especially in nonsmokers. There is evidence for increased lung cancer risk in industrial radiation workers, especially those who process plutonium and may inhale radioactive particles. There does not seem to be an increased risk of lung cancer in healthcare workers who perform fluoroscopic procedures. High-dose ionizing radiation exposure causes pneumonitis and fibrosis, and more research is needed to develop mitigators to improve outcomes in nuclear catastrophes. Long-term, low-dose occupational radiation may increase lung cancer risk. More research to better define this risk could lead to improved safety protocols and screening programs.

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice.

PubMed

Ramsey, Kathryn A; Larcombe, Alexander N; Sly, Peter D; Zosky, Graeme R

2013-02-18

Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations.

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

PubMed Central

2013-01-01

Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

Biological Bases for Radiation Adaptive Responses in the Lung

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

Scott, Bobby R.; Lin, Yong; Wilder, Julie

2015-03-01

Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

Local noise reduction for emphysema scoring in low-dose CT images

NASA Astrophysics Data System (ADS)

Schilham, Arnold; Prokop, Mathias; Gietema, Hester; van Ginneken, Bram

2005-04-01

Computed Tomography (CT) has become the new reference standard for quantification of emphysema. The most popular measure for emphysema derived from CT is the Pixel Index (PI), which expresses the fraction of the lung volume with abnormally low intensity values. As PI is calculated from a single, fixed threshold on intensity, this measure is strongly influenced by noise. This effect shows up clearly when comparing the PI score for a high-dose scan to the PI score for a low-dose (i.e. noisy) scan of the same subject. This paper presents a class of noise filters that make use of a local noise estimate to specify the filtering strength: Local Noise Variance Weighted Averaging (LNVWA). The performance of the filter is assessed by comparing high-dose and low-dose PI scores for 11 subjects. LNVWA improves the reproducibility of high-dose PI scores: For an emphysema threshold of -910 HU, the root-mean-square difference in PI score drops from 10% of the lung volume to 3.3% of the lung volume if LNVWA is used.

A feasibility study on the use of phantoms with statistical lung masses for determining the uncertainty in the dose absorbed by the lung from broad beams of incident photons and neutrons.

PubMed

Khankook, Atiyeh Ebrahimi; Hakimabad, Hashem Miri; Motavalli, Laleh Rafat

2017-05-01

Computational models of the human body have gradually become crucial in the evaluation of doses absorbed by organs. However, individuals may differ considerably in terms of organ size and shape. In this study, the authors sought to determine the energy-dependent standard deviations due to lung size of the dose absorbed by the lung during external photon and neutron beam exposures. One hundred lungs with different masses were prepared and located in an adult male International Commission on Radiological Protection (ICRP) reference phantom. Calculations were performed using the Monte Carlo N-particle code version 5 (MCNP5). Variation in the lung mass caused great uncertainty: ~90% for low-energy broad parallel photon beams. However, for high-energy photons, the lung-absorbed dose dependency on the anatomical variation was reduced to <1%. In addition, the results obtained indicated that the discrepancy in the lung-absorbed dose varied from 0.6% to 8% for neutron beam exposure. Consequently, the relationship between absorbed dose and organ volume was found to be significant for low-energy photon sources, whereas for higher energy photon sources the organ-absorbed dose was independent of the organ volume. In the case of neutron beam exposure, the maximum discrepancy (of 8%) occurred in the energy range between 0.1 and 5 MeV. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

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

Huang, Q; Zhang, M; Chen, T

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Protonmore » and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.« less

Results of the two incidence screenings in the National Lung Screening Trial.

PubMed

Aberle, Denise R; DeMello, Sarah; Berg, Christine D; Black, William C; Brewer, Brenda; Church, Timothy R; Clingan, Kathy L; Duan, Fenghai; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine A; Gierada, David S; Jain, Amanda; Jones, Gordon C; Mahon, Irene; Marcus, Pamela M; Rathmell, Joshua M; Sicks, JoRean

2013-09-05

The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

PubMed Central

Furukawa, Katsuro; Matsumoto, Keitaro; Nagayasu, Takeshi; Yamamoto-Fukuda, Tomomi; Tobinaga, Shuichi; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Nanashima, Atsushi; Obatake, Masayuki; Koji, Takehiko

2013-01-01

Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth. PMID:24610965

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat.

PubMed

Furukawa, Katsuro; Matsumoto, Keitaro; Nagayasu, Takeshi; Yamamoto-Fukuda, Tomomi; Tobinaga, Shuichi; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Nanashima, Atsushi; Obatake, Masayuki; Koji, Takehiko

2013-12-28

Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.

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

PubMed

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

2018-01-01

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

WE-D-207-03: CT Protocols for Screening and the ACR Designated Lung Screening Program

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

McNitt-Gray, M.

2015-06-15

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

PubMed

Yu, I J; Song, K S; Chang, H K; Han, J H; Kim, K J; Chung, Y H; Maeng, S H; Park, S H; Han, K T; Chung, K H; Chung, H K

2001-09-01

To investigate the disease process of pneumoconiosis induced by welding-fume exposure, a lung fibrosis model was established by building a stainless steel arc welding fume generation system and exposing male Sprague-Dawley rats for 90 days. The rats were exposed to welding fumes with concentrations of 57-67 mg/m3 (low dose) and 105-118 mg/m3 (high dose) total suspended particulates for 2 h per day in an inhalation chamber for 90 days. The concentrations of the main metals, Fe, Mn, Cr, and Ni, were measured in the welding fumes, plus the gaseous compounds, including nitrous gases and ozone, were monitored. During the exposure period, the animals were sacrificed after the initial 2-h exposure and after 15, 30, 60, and 90 days. Histopathological examinations were conducted on the animals' upper respiratory tract, including the nasal pathway and conducting airway, plus the gas exchange region, including the alveolar ducts, alveolar sacs, and alveoli. When compared to the control group, the lung weights did not increase significantly in the low-dose group, yet in the high-dose group there was a significant increase from day 15 to day 90. The histopathological examination combined with fibrosis-specific staining (Masson's trichrome) indicated that the lungs in the low-dose group did not exhibit any progressive fibrotic changes. Whereas, the lungs in the high-dose group exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Accordingly, it would appear that a significant dose of welding-fume exposure was required to induce lung fibrosis.

Ultra-Shallow Junctions Fabrication by Plasma Immersion Implantation on PULSION registered Followed by Laser Thermal Processing

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

Torregrosa, Frank; Etienne, Hasnaa; Sempere, Guillaume

In order to achieve the requirements for P+/N junctions for <45 nm ITRS nodes, ultra low energy and high dose implantations are needed. Classical beamline implantation is now limited in low energies, compared to Plasma Immersion Ion Implantation (PIII) which efficiency is no more to prove for the realization of Ultra-Shallow Junctions (USJ) in semiconductor applications : this technique allows to get ultimate shallow profiles (as implanted) due to no lower limitation of energy and high dose rate. Electrical activation is also a big issue since it has to afford high electrical activation rate with very low diffusion. Laser annealingmore » is one of the candidates for the 45 nm node. This paper presents electrical and physico-chemical characterizations of junctions realized with BF3 PIII followed by laser thermal processing with aim to obtain ultra-shallow junctions. Different implantation conditions (acceleration voltage/dose) and laser conditions (laser types, fluence/number of shots) are used for this study. Pre-amorphization is also used to confine the junction depth, and is shown to have a positive effect on junction depth but leads in higher junction leakage due to the remaining of EOR defects. The characterization is done using Optical characterization tool (SEMILAB) for sheet resistance and junction leakage measurements. SIMS is used for Boron profile and junction depth.« less

NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction.

PubMed

Wennberg, Berit M; Baumann, Pia; Gagliardi, Giovanna; Nyman, Jan; Drugge, Ninni; Hoyer, Morten; Traberg, Anders; Nilsson, Kristina; Morhed, Elisabeth; Ekberg, Lars; Wittgren, Lena; Lund, Jo-Åsmund; Levin, Nina; Sederholm, Christer; Lewensohn, Rolf; Lax, Ingmar

2011-05-01

In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/β = 3 Gy was used and the USC parameters used were: α/β = 3 Gy, D(0) = 1.0 Gy, [Formula: see text] = 10, α = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. NTCP analysis with the LKB-model using parameters m = 0.4, D(50) = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D(50) = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.

Potential Treatment of Inflammatory and Proliferative Diseases by Ultra-Low Doses of Ionizing Radiations

PubMed Central

Sanders, Charles L.

2012-01-01

Ultra-low doses and dose- rates of ionizing radiation are effective in preventing disease which suggests that they also may be effective in treating disease. Limited experimental and anecdotal evidence indicates that low radiation doses from radon in mines and spas, thorium-bearing monazite sands and enhanced radioactive uranium ore obtained from a natural geological reactor may be useful in treating many inflammatory conditions and proliferative disorders, including cancer. Optimal therapeutic applications were identified via a literature survey as dose-rates ranging from 7 to 11μGy/hr or 28 to 44 times world average background rates. Rocks from an abandoned uranium mine in Utah were considered for therapeutic application and were examined by γ-ray and laser-induced breakdown fluorescence spectroscopy. The rocks showed the presence of transuranics and fission products with a γ-ray energy profile similar to aged spent uranium nuclear fuel (93% dose due to β particles and 7% due to γ rays). Mud packs of pulverized uranium ore rock dust in sealed plastic bags delivering bag surface β,γ dose-rates of 10–450 μGy/h were used with apparent success to treat several inflammatory and proliferative conditions in humans. PMID:23304108

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

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

Yaparpalvi, R; Mynampati, D; Kuo, H

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm may very well be warranted.« less

Influence of Sinogram-Affirmed Iterative Reconstruction on Computed Tomography-Based Lung Volumetry and Quantification of Pulmonary Emphysema.

PubMed

Baumueller, Stephan; Hilty, Regina; Nguyen, Thi Dan Linh; Weder, Walter; Alkadhi, Hatem; Frauenfelder, Thomas

2016-01-01

The purpose of this study was to evaluate the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on quantification of lung volume and pulmonary emphysema in low-dose chest computed tomography compared with filtered back projection (FBP). Enhanced or nonenhanced low-dose chest computed tomography was performed in 20 patients with chronic obstructive pulmonary disease (group A) and in 20 patients without lung disease (group B). Data sets were reconstructed with FBP and SAFIRE strength levels 3 to 5. Two readers semiautomatically evaluated lung volumes and automatically quantified pulmonary emphysema, and another assessed image quality. Radiation dose parameters were recorded. Lung volume between FBP and SAFIRE 3 to 5 was not significantly different among both groups (all P > 0.05). When compared with those of FBP, total emphysema volume was significantly lower among reconstructions with SAFIRE 4 and 5 (mean difference, 0.56 and 0.79 L; all P < 0.001). There was no nondiagnostic image quality. Sinogram-affirmed iterative reconstruction does not alter lung volume measurements, although quantification of lung emphysema is affected at higher strength levels.

Noninvasive Computed Tomography–based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial

PubMed Central

Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M.; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A.; Bartholmai, Brian J.

2015-01-01

Rationale: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. Objectives: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. Methods: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. Measurements and Main Results: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. Conclusions: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas. PMID:26052977

Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

PubMed

Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M; Rajagopalan, Srinivasan; Karwoski, Ronald A; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A; Bartholmai, Brian J; Peikert, Tobias

2015-09-15

Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Rapid biosynthesis of silver nanoparticles using Crotalaria verrucosa leaves against the dengue vector Aedes aegypti: what happens around? An analysis of dragonfly predatory behaviour after exposure at ultra-low doses.

PubMed

Murugan, Kadarkarai; Sanoopa, C P; Madhiyazhagan, Pari; Dinesh, Devakumar; Subramaniam, Jayapal; Panneerselvam, Chellasamy; Roni, Mathath; Suresh, Udaiyan; Nicoletti, Marcello; Alarfaj, Abdullah A; Munusamy, Murugan A; Higuchi, Akon; Kumar, Suresh; Perumalsamy, Haribalan; Ahn, Young-Joon; Benelli, Giovanni

2016-01-01

Aedes aegypti is a primary vector of dengue, a mosquito-borne viral disease infecting 50-100 million people every year. Here, we biosynthesised mosquitocidal silver nanoparticles (AgNP) using the aqueous leaf extract of Crotalaria verrucosa. The green synthesis of AgNP was studied by UV-vis spectroscopy, SEM, EDX and FTIR. C. verrucosa-synthesised AgNPs were toxic against A. aegypti larvae and pupae. LC50 of AgNP ranged from 3.496 ppm (I instar larvae) to 17.700 ppm (pupae). Furthermore, we evaluated the predatory efficiency of dragonfly nymphs, Brachydiplax sobrina, against II and III instar larvae of A. aegypti in an aquatic environment contaminated with ultra-low doses of AgNP. Under standard laboratory conditions, predation after 24 h was 87.5% (II) and 54.7% (III). In an AgNP-contaminated environment, predation was 91 and 75.5%, respectively. Overall, C. verrucosa-synthesised AgNP could be employed at ultra-low doses to reduce larval population of dengue vectors enhancing predation rates of dragonfly nymphs.

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.

PubMed

Hsu, Kuang-Hung; Tsui, Ke-Hung; Hsu, Ling-I; Chiou, Hung-Yi; Chen, Chien-Jen

2017-05-01

Background: Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence. Methods: We followed 1,300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazards model was performed. Results: The results demonstrated that participants with either the primary methylation index [monomethylarsonic acid (MMA)/InAs] or the secondary methylation index [dimethylarsenic acid (DMA)/MMA] lower than their respective median values were at a higher risk of lung cancer (HRs from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100,000 (year -1 ) to 467.4/100,000 (year -1 ) for residents with low methylation capacity and from 0 to 158.5/100,000 (year -1 ) for residents with high methylation capacity when the arsenic exposure dose increased from 2 to 10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < 0.05 and P < 0.05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylators was not statistically significant. Conclusions: Hypomethylation responses to InAs exposure may dose dependently increase lung cancer occurrence. Impact: The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(5); 756-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

ClinicalTrials.gov

2017-06-29

Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

SU-E-J-86: Functional Conformal Planning for Stereotactic Body Radiation Therapy with CT-Pulmonary Ventilation Imaging

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

Kurosawa, T; Moriya, S; Sato, M

2015-06-15

Purpose: To evaluate the functional planning using CT-pulmonary ventilation imaging for conformal SBRT. Methods: The CT-pulmonary ventilation image was generated using the Jacobian metric in the in-house program with the NiftyReg software package. Using the ventilation image, the normal lung was split into three lung regions for functionality (high, moderate and low). The anatomical plan (AP) and functional plan (FP) were made for ten lung SBRT patients. For the AP, the beam angles were optimized with the dose-volume constraints for the normal lung sparing and the PTV coverage. For the FP, the gantry angles were also optimized with the additionalmore » constraint for high functional lung. The MLC aperture shapes were adjusted to the PTV with the additional 5 mm margin. The dosimetric parameters for PTV, the functional volumes, spinal cord and so on were compared in both plans. Results: Compared to the AP, the FP showed better dose sparing for high- and moderate-functional lungs with similar PTV coverage while not taking care of the low functional lung (High:−12.9±9.26% Moderate: −2.0±7.09%, Low: +4.1±12.2%). For the other normal organs, the FP and AP showed similar dose sparing in the eight patients. However, the FP showed that the maximum doses for spinal cord were increased with the significant increment of 16.4Gy and 21.0Gy in other two patients, respectively. Because the beam direction optimizer chose the unexpected directions passing through the spinal cord. Conclusion: Even the functional conformal SBRT can selectively reduce high- and moderatefunctional lung while keeping the PTV coverage. However, it would be careful that the optimizer would choose unexpected beam angles and the dose sparing for the other normal organs can be worse. Therefore, the planner needs to control the dose-volume constraints and also limit the beam angles in order to achieve the expected dose sparing and coverage.« less

Lack of soluble tumor necrosis factor alpha receptor 1 and 2 and interleukin-1beta compartmentalization in lungs of mice after a single intratracheal inoculation with live Porphyromonas gingivalis.

PubMed

Nemec, Ana; Pavlica, Zlatko; Svete, Alenka Nemec; Erzen, Damijan; Crossley, David A; Petelin, Milan

2009-09-01

Porphyromonas gingivalis aspiration pneumonia induces local and systemic cytokine responses, but the dynamic of the immune response following lung exposure to live P. gingivalis is poorly understood. Groups of 50 12-week-old male BALB/c mice were inoculated intratracheally with live P. gingivalis ATCC 33277 using low dose (2 x 10(5) colony-forming units [CFU]), high dose (2.9 x 10(9) CFU), or phosphate-buffered saline (PBS; sham-inoculated), and the 3 groups were sacrificed at 2, 6, 24, 72, 168 hours. Lung and serum samples were collected for tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (sTNFRs), interleukin (IL)-1beta, and IL-6 analysis and lung histology. Pneumonia, only observed in the high-dose group, was associated with an early increase in lung TNF-alpha, IL-1beta, and IL-6, whereas no significant changes were observed in lung sTNFRs. Serum sTNFRs were significantly increased in high-dose animals at all times. IL-1beta elevation occurred earlier in serum than in lungs. IL-1beta was also significantly elevated in serum from low-dose animals at 6 hours. Serum IL-6 and sTNFRs remained raised at 7 days, whereas all other measured cytokines returned to basal levels with resolution of pneumonia. Development of pneumonia is dependent on the P. gingivalis dose; however, part of the cytokine response is unique to the systemic compartment, even in animals that do not develop pneumonia.

National Lung Screening Trial: Questions and Answers

Cancer.gov

Learn the results of the National Lung Screening Trial (NLST), which compared two ways of detecting lung cancer: low-dose helical (spiral) computed tomography and standard chest X-ray, for their effects on lung cancer death rates in a high-risk population.

Low-dose computed tomography volumetry for subtyping chronic lung allograft dysfunction.

PubMed

Saito, Tomohito; Horie, Miho; Sato, Masaaki; Nakajima, Daisuke; Shoushtarizadeh, Hassan; Binnie, Matthew; Azad, Sassan; Hwang, David M; Machuca, Tiago N; Waddell, Thomas K; Singer, Lianne G; Cypel, Marcelo; Liu, Mingyao; Paul, Narinder S; Keshavjee, Shaf

2016-01-01

The long-term success of lung transplantation is challenged by the development of chronic lung allograft dysfunction (CLAD) and its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). However, the current diagnostic criteria for CLAD subtypes rely on total lung capacity (TLC), which is not always measured during routine post-transplant assessment. Our aim was to investigate the utility of low-dose 3-dimensional computed tomography (CT) lung volumetry for differentiating RAS from BOS. This study was a retrospective evaluation of 63 patients who had developed CLAD after bilateral lung or heart‒lung transplantation between 2006 and 2011, including 44 BOS and 19 RAS cases. Median post-transplant follow-up was 65 months in BOS and 27 months in RAS. The median interval between baseline and the disease-onset time-point for CT volumetry was 11 months in both BOS and RAS. Chronologic changes and diagnostic accuracy of CT lung volume (measured as percent of baseline) were investigated. RAS showed a significant decrease in CT lung volume at disease onset compared with baseline (mean 3,916 ml vs 3,055 ml when excluding opacities, p < 0.0001), whereas BOS showed no significant post-transplant change (mean 4,318 ml vs 4,396 ml, p = 0.214). The area under the receiver operating characteristic curve of CT lung volume for differentiating RAS from BOS was 0.959 (95% confidence interval 0.912 to 1.01, p < 0.0001) and the calculated accuracy was 0.938 at a threshold of 85%. In bilateral lung or heart‒lung transplant patients with CLAD, low-dose CT volumetry is a useful tool to differentiate patients who develop RAS from those who develop BOS. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Recommendations for dose calculations of lung cancer treatment plans treated with stereotactic ablative body radiotherapy (SABR)

NASA Astrophysics Data System (ADS)

Devpura, S.; Siddiqui, M. S.; Chen, D.; Liu, D.; Li, H.; Kumar, S.; Gordon, J.; Ajlouni, M.; Movsas, B.; Chetty, I. J.

2014-03-01

The purpose of this study was to systematically evaluate dose distributions computed with 5 different dose algorithms for patients with lung cancers treated using stereotactic ablative body radiotherapy (SABR). Treatment plans for 133 lung cancer patients, initially computed with a 1D-pencil beam (equivalent-path-length, EPL-1D) algorithm, were recalculated with 4 other algorithms commissioned for treatment planning, including 3-D pencil-beam (EPL-3D), anisotropic analytical algorithm (AAA), collapsed cone convolution superposition (CCC), and Monte Carlo (MC). The plan prescription dose was 48 Gy in 4 fractions normalized to the 95% isodose line. Tumors were classified according to location: peripheral tumors surrounded by lung (lung-island, N=39), peripheral tumors attached to the rib-cage or chest wall (lung-wall, N=44), and centrally-located tumors (lung-central, N=50). Relative to the EPL-1D algorithm, PTV D95 and mean dose values computed with the other 4 algorithms were lowest for "lung-island" tumors with smallest field sizes (3-5 cm). On the other hand, the smallest differences were noted for lung-central tumors treated with largest field widths (7-10 cm). Amongst all locations, dose distribution differences were most strongly correlated with tumor size for lung-island tumors. For most cases, convolution/superposition and MC algorithms were in good agreement. Mean lung dose (MLD) values computed with the EPL-1D algorithm were highly correlated with that of the other algorithms (correlation coefficient =0.99). The MLD values were found to be ~10% lower for small lung-island tumors with the model-based (conv/superposition and MC) vs. the correction-based (pencil-beam) algorithms with the model-based algorithms predicting greater low dose spread within the lungs. This study suggests that pencil beam algorithms should be avoided for lung SABR planning. For the most challenging cases, small tumors surrounded entirely by lung tissue (lung-island type), a Monte-Carlo-based algorithm may be warranted.

National Lung Screening Trial (NLST)

Cancer.gov

The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

Lung Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

Lung Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Learn more about tests to detect lung cancer and their potential benefits and harms in this expert-reviewed summary.

Multiple image x-radiography for functional lung imaging

NASA Astrophysics Data System (ADS)

Aulakh, G. K.; Mann, A.; Belev, G.; Wiebe, S.; Kuebler, W. M.; Singh, B.; Chapman, D.

2018-01-01

Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Comparison of low- and ultralow-dose computed tomography protocols for quantitative lung and airway assessment.

PubMed

Hammond, Emily; Sloan, Chelsea; Newell, John D; Sieren, Jered P; Saylor, Melissa; Vidal, Craig; Hogue, Shayna; De Stefano, Frank; Sieren, Alexa; Hoffman, Eric A; Sieren, Jessica C

2017-09-01

Quantitative computed tomography (CT) measures are increasingly being developed and used to characterize lung disease. With recent advances in CT technologies, we sought to evaluate the quantitative accuracy of lung imaging at low- and ultralow-radiation doses with the use of iterative reconstruction (IR), tube current modulation (TCM), and spectral shaping. We investigated the effect of five independent CT protocols reconstructed with IR on quantitative airway measures and global lung measures using an in vivo large animal model as a human subject surrogate. A control protocol was chosen (NIH-SPIROMICS + TCM) and five independent protocols investigating TCM, low- and ultralow-radiation dose, and spectral shaping. For all scans, quantitative global parenchymal measurements (mean, median and standard deviation of the parenchymal HU, along with measures of emphysema) and global airway measurements (number of segmented airways and pi10) were generated. In addition, selected individual airway measurements (minor and major inner diameter, wall thickness, inner and outer area, inner and outer perimeter, wall area fraction, and inner equivalent circle diameter) were evaluated. Comparisons were made between control and target protocols using difference and repeatability measures. Estimated CT volume dose index (CTDIvol) across all protocols ranged from 7.32 mGy to 0.32 mGy. Low- and ultralow-dose protocols required more manual editing and resolved fewer airway branches; yet, comparable pi10 whole lung measures were observed across all protocols. Similar trends in acquired parenchymal and airway measurements were observed across all protocols, with increased measurement differences using the ultralow-dose protocols. However, for small airways (1.9 ± 0.2 mm) and medium airways (5.7 ± 0.4 mm), the measurement differences across all protocols were comparable to the control protocol repeatability across breath holds. Diameters, wall thickness, wall area fraction, and equivalent diameter had smaller measurement differences than area and perimeter measurements. In conclusion, the use of IR with low- and ultralow-dose CT protocols with CT volume dose indices down to 0.32 mGy maintains selected quantitative parenchymal and airway measurements relevant to pulmonary disease characterization. © 2017 American Association of Physicists in Medicine.

The effect of radiation dose reduction on computer-aided detection (CAD) performance in a low-dose lung cancer screening population.

PubMed

Young, Stefano; Lo, Pechin; Kim, Grace; Brown, Matthew; Hoffman, John; Hsu, William; Wahi-Anwar, Wasil; Flores, Carlos; Lee, Grace; Noo, Frederic; Goldin, Jonathan; McNitt-Gray, Michael

2017-04-01

Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population. The raw projection data files were collected from 481 patients who underwent low-dose screening CT exams at our institution as part of the National Lung Screening Trial (NLST). All scans were performed on a multidetector scanner (Sensation 64, Siemens Healthcare, Forchheim Germany) according to the NLST protocol, which called for a fixed tube current scan of 25 effective mAs for standard-sized patients and 40 effective mAs for larger patients. The raw projection data were input to a reduced-dose simulation software to create simulated reduced-dose scans corresponding to 50% and 25% of the original protocols. All raw data files were reconstructed at the scanner with 1 mm slice thickness and B50 kernel. The lungs were segmented semi-automatically, and all images and segmentations were input to an in-house CAD algorithm trained on higher dose scans (75-300 mAs). CAD findings were compared to a reference standard generated by an experienced reader. Nodule- and patient-level sensitivities were calculated along with false positives per scan, all of which were evaluated in terms of the relative change with respect to dose. Nodules were subdivided based on size and solidity into categories analogous to the LungRADS assessment categories, and sub-analyses were performed. From the 481 patients in this study, 82 had at least one nodule (prevalence of 17%) and 399 did not (83%). A total of 118 nodules were identified. Twenty-seven nodules (23%) corresponded to LungRADS category 4 based on size and composition, while 18 (15%) corresponded to LungRADS category 3 and 73 (61%) corresponded to LungRADS category 2. For solid nodules ≥8 mm, patient-level median sensitivities were 100% at all three dose levels, and mean sensitivities were 72%, 63%, and 63% at original, 50%, and 25% dose, respectively. Overall mean patient-level sensitivities for nodules ranging from 3 to 45 mm were 38%, 37%, and 38% at original, 50%, and 25% dose due to the prevalence of smaller nodules and nonsolid nodules in our reference standard. The mean false-positive rates were 3, 5, and 13 per case. CAD sensitivity decreased very slightly for larger nodules as dose was reduced, indicating that reducing the dose to 50% of original levels may be investigated further for use in CT screening. However, the effect of dose was small relative to the effect of the nodule size and solidity characteristics. The number of false positives per scan increased substantially at 25% dose, illustrating the importance of tuning CAD algorithms to very challenging, high-noise screening exams. © 2017 American Association of Physicists in Medicine.

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

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

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center.

PubMed

Chong, Semin; Lee, Kyung Soo; Chung, Myung Jin; Kim, Tae Sung; Kim, Hojoong; Kwon, O Jung; Choi, Yoon-Ho; Rhee, Chong H

2005-06-01

To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with >or=45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (>or=20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.

Fan-shaped complete block on helical tomotherapy for esophageal cancer: a phantom study.

PubMed

Chang, Chiu-Han; Mok, Greta S P; Shueng, Pei-Wei; Yeh, Hsin-Pei; Shiau, An-Cheng; Tien, Hui-Ju; Lin, Chi-Ta; Wu, Tung-Hsin

2015-01-01

Radiation pneumonitis (RP) is a common complication for radiotherapy of esophageal cancer and is associated with the low dose irradiated lung volume. This study aims to reduce the mean lung dose (MLD) and the relative lung volume at 20 Gy (V 20) and at low dose region using various designs of the fan-shaped complete block (FSCB) in helical tomotherapy. Hypothetical esophageal tumor was delineated on an anthropomorphic phantom. The FSCB was defined as the fan-shaped radiation restricted area located in both lungs. Seven treatment plans were performed with nonblock design and FSCB with different fan angles, that is, from 90° to 140°, with increment of 10°. The homogeneous index, conformation number, MLD, and the relative lung volume receiving more than 5, 10, 15, and 20 Gy (V 5, V 10, V 15, and V 20) were determined for each treatment scheme. There was a substantial reduction in the MLD, V 5, V 10, V 15, and V 20 when using different types of FSCB as compared to the nonblock design. The reduction of V 20, V 15, V 10, and V 5 was 6.3%-8.6%, 16%-23%, 42%-57%, and 42%-66% for FSCB 90°-140°, respectively. The use of FSCB in helical tomotherapy is a promising method to reduce the MLD, V 20, and relative lung volume in low dose region, especially in V 5 and V 10 for esophageal cancer.

Probability of cancer in pulmonary nodules detected on first screening CT.

PubMed

McWilliams, Annette; Tammemagi, Martin C; Mayo, John R; Roberts, Heidi; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Martel, Simon; Laberge, Francis; Gingras, Michel; Atkar-Khattra, Sukhinder; Berg, Christine D; Evans, Ken; Finley, Richard; Yee, John; English, John; Nasute, Paola; Goffin, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Johnston, Michael R; Manos, Daria; Nicholas, Garth; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Tremblay, Alain; Burrowes, Paul; MacEachern, Paul; Bhatia, Rick; Tsao, Ming-Sound; Lam, Stephen

2013-09-05

Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Terminate Lung Cancer (TLC) Study - A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky

PubMed Central

Cardarelli, Roberto; Reese, David; Roper, Karen L.; Cardarelli, Kathryn; Feltner, Frances J.; Studts, Jamie L.; Knight, Jennifer R.; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

2017-01-01

For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region. PMID:27866066

The validation of tomotherapy dose calculations in low-density lung media

NASA Astrophysics Data System (ADS)

Chaudhari, Summer R.; Pechenaya, Olga L.; Goddu, S. Murty; Mutic, Sasa; Rangaraj, Dharanipathy; Bradley, Jeffrey D.; Low, Daniel

2009-04-01

The dose-calculation accuracy of the tomotherapy Hi-Art II® (Tomotherapy, Inc., Madison, WI) treatment planning system (TPS) in the presence of low-density lung media was investigated. In this evaluation, a custom-designed heterogeneous phantom mimicking the mediastinum geometry was used. Gammex LN300 and balsa wood were selected as two lung-equivalent materials with different densities. Film analysis and ionization chamber measurements were performed. Treatment plans for esophageal cancers were used in the evaluation. The agreement between the dose calculated by the TPS and the dose measured via ionization chambers was, in most cases, within 0.8%. Gamma analysis using 3% and 3 mm criteria for radiochromic film dosimetry showed that 98% and 95% of the measured dose distribution had passing gamma values <=1 for LN300 and balsa wood, respectively. For a homogeneous water-equivalent phantom, 95% of the points passed the gamma test. It was found that for the interface between the low-density medium and water-equivalent medium, the TPS calculated the dose distribution within acceptable limits. The phantom developed for this work enabled detailed quality-assurance testing under realistic conditions with heterogeneous media.

The validation of tomotherapy dose calculations in low-density lung media.

PubMed

Chaudhari, Summer R; Pechenaya, Olga L; Goddu, S Murty; Mutic, Sasa; Rangaraj, Dharanipathy; Bradley, Jeffrey D; Low, Daniel

2009-04-21

The dose-calculation accuracy of the tomotherapy Hi-Art II(R) (Tomotherapy, Inc., Madison, WI) treatment planning system (TPS) in the presence of low-density lung media was investigated. In this evaluation, a custom-designed heterogeneous phantom mimicking the mediastinum geometry was used. Gammex LN300 and balsa wood were selected as two lung-equivalent materials with different densities. Film analysis and ionization chamber measurements were performed. Treatment plans for esophageal cancers were used in the evaluation. The agreement between the dose calculated by the TPS and the dose measured via ionization chambers was, in most cases, within 0.8%. Gamma analysis using 3% and 3 mm criteria for radiochromic film dosimetry showed that 98% and 95% of the measured dose distribution had passing gamma values < or =1 for LN300 and balsa wood, respectively. For a homogeneous water-equivalent phantom, 95% of the points passed the gamma test. It was found that for the interface between the low-density medium and water-equivalent medium, the TPS calculated the dose distribution within acceptable limits. The phantom developed for this work enabled detailed quality-assurance testing under realistic conditions with heterogeneous media.

WE-FG-207B-07: Feasibility of Low Dose Lung Cancer Screening with a Whole-Body Photon Counting CT: First Human Results

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

Symons, R; Cork, T; Folio, L

2016-06-15

Purpose: To evaluate the feasibility of using a whole-body photon counting detector (PCD) CT scanner for low dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Methods: Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom and 2 human volunteers were acquired. Phantom images were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp), while human images were acquired at vendor recommended low-dose lung cancer screening settings. EID and PCD images were compared for quantitative Hounsfield unit accuracy, noise levels, and contrast-to-noisemore » ratios (CNR) for detection of ground-glass nodules (GGNs) and emphysema. Results: The PCD Hounsfield unit accuracy was better for water at all scan parameters, and for lung, GGN and emphysema equivalent regions of interest (ROIs) at 1.5 and 0.75 mGy. PCD attenuation accuracy was more consistent for all scan parameters (all P<0.01), while Hounsfield units for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P<0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2±0.3 vs 15.8±0.2, P=0.03; 16.1±0.3 vs 18.0±0.4, P=0.003; and 16.1±0.3 vs 17.9±0.3, P=0.001, respectively), resulting in superior CNR for the detection of GGNs and emphysema at 100 and 80 kVp. Significantly lower PCD noise levels were confirmed in volunteer images. Conclusion: PCD provided better Hounsfield unit accuracy for lung, ground-glass, and emphysema-equivalent foams at 1.5 and 0.75 mGy with less variability than EID. Additionally, PCD showed less noise, and higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.« less

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.

Frequency and distribution of incidental findings deemed appropriate for S modifier designation on low-dose CT in a lung cancer screening program.

PubMed

Reiter, Michael J; Nemesure, Allison; Madu, Ezemonye; Reagan, Lisa; Plank, April

2018-06-01

To describe the frequency, distribution and reporting patterns of incidental findings receiving the Lung-RADS S modifier on low-dose chest computed tomography (CT) among lung cancer screening participants. This retrospective investigation included 581 individuals who received baseline low-dose chest CT for lung cancer screening between October 2013 and June 2017 at a single center. Incidental findings resulting in assignment of Lung-RADS S modifier were recorded as were incidental abnormalities detailed within the body of the radiology report only. A subset of 60 randomly selected CTs was reviewed by a second (blinded) radiologist to evaluate inter-rater variability of Lung-RADS reporting. A total of 261 (45%) participants received the Lung-RADS S modifier on baseline CT with 369 incidental findings indicated as potentially clinically significant. Coronary artery calcification was most commonly reported, accounting for 182 of the 369 (49%) findings. An additional 141 incidentalomas of the same types as these 369 findings were described in reports but were not labelled with the S modifier. Therefore, as high as 69% (402 of 581) of participants could have received the S modifier if reporting was uniform. Inter-radiologist concordance of S modifier reporting in a subset of 60 participants was poor (42% agreement, kappa = 0.2). Incidental findings are commonly identified on chest CT for lung cancer screening, yet reporting of the S modifier within Lung-RADS is inconsistent. Specific guidelines are necessary to better define potentially clinically significant abnormalities and to improve reporting uniformity. Copyright © 2018 Elsevier B.V. All rights reserved.

Underestimation of Low-Dose Radiation in Treatment Planning of Intensity-Modulated Radiotherapy

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

Jang, Si Young; Liu, H. Helen; Mohan, Radhe

2008-08-01

Purpose: To investigate potential dose calculation errors in the low-dose regions and identify causes of such errors for intensity-modulated radiotherapy (IMRT). Methods and Materials: The IMRT treatment plans of 23 patients with lung cancer and mesothelioma were reviewed. Of these patients, 15 had severe pulmonary complications after radiotherapy. Two commercial treatment-planning systems (TPSs) and a Monte Carlo system were used to calculate and compare dose distributions and dose-volume parameters of the target volumes and critical structures. The effect of tissue heterogeneity, multileaf collimator (MLC) modeling, beam modeling, and other factors that could contribute to the differences in IMRT dose calculationsmore » were analyzed. Results: In the commercial TPS-generated IMRT plans, dose calculation errors primarily occurred in the low-dose regions of IMRT plans (<50% of the radiation dose prescribed for the tumor). Although errors in the dose-volume histograms of the normal lung were small (<5%) above 10 Gy, underestimation of dose <10 Gy was found to be up to 25% in patients with mesothelioma or large target volumes. These errors were found to be caused by inadequate modeling of MLC transmission and leaf scatter in commercial TPSs. The degree of low-dose errors depends on the target volumes and the degree of intensity modulation. Conclusions: Secondary radiation from MLCs contributes a significant portion of low dose in IMRT plans. Dose underestimation could occur in conventional IMRT dose calculations if such low-dose radiation is not properly accounted for.« less

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

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

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

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

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 CTmore » 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.« less

CT of the chest with model-based, fully iterative reconstruction: comparison with adaptive statistical iterative reconstruction.

PubMed

Ichikawa, Yasutaka; Kitagawa, Kakuya; Nagasawa, Naoki; Murashima, Shuichi; Sakuma, Hajime

2013-08-09

The recently developed model-based iterative reconstruction (MBIR) enables significant reduction of image noise and artifacts, compared with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP). The purpose of this study was to evaluate lesion detectability of low-dose chest computed tomography (CT) with MBIR in comparison with ASIR and FBP. Chest CT was acquired with 64-slice CT (Discovery CT750HD) with standard-dose (5.7 ± 2.3 mSv) and low-dose (1.6 ± 0.8 mSv) conditions in 55 patients (aged 72 ± 7 years) who were suspected of lung disease on chest radiograms. Low-dose CT images were reconstructed with MBIR, ASIR 50% and FBP, and standard-dose CT images were reconstructed with FBP, using a reconstructed slice thickness of 0.625 mm. Two observers evaluated the image quality of abnormal lung and mediastinal structures on a 5-point scale (Score 5 = excellent and score 1 = non-diagnostic). The objective image noise was also measured as the standard deviation of CT intensity in the descending aorta. The image quality score of enlarged mediastinal lymph nodes on low-dose MBIR CT (4.7 ± 0.5) was significantly improved in comparison with low-dose FBP and ASIR CT (3.0 ± 0.5, p = 0.004; 4.0 ± 0.5, p = 0.02, respectively), and was nearly identical to the score of standard-dose FBP image (4.8 ± 0.4, p = 0.66). Concerning decreased lung attenuation (bulla, emphysema, or cyst), the image quality score on low-dose MBIR CT (4.9 ± 0.2) was slightly better compared to low-dose FBP and ASIR CT (4.5 ± 0.6, p = 0.01; 4.6 ± 0.5, p = 0.01, respectively). There were no significant differences in image quality scores of visualization of consolidation or mass, ground-glass attenuation, or reticular opacity among low- and standard-dose CT series. Image noise with low-dose MBIR CT (11.6 ± 1.0 Hounsfield units (HU)) were significantly lower than with low-dose ASIR (21.1 ± 2.6 HU, p < 0.0005), low-dose FBP CT (30.9 ± 3.9 HU, p < 0.0005), and standard-dose FBP CT (16.6 ± 2.3 HU, p < 0.0005). MBIR shows greater potential than ASIR for providing diagnostically acceptable low-dose CT without compromising image quality. With radiation dose reduction of >70%, MBIR can provide equivalent lesion detectability of standard-dose FBP CT.

Inhibition of the biosynthesis of prostaglandin E2 by low dose aspirin: implications for adenocarcinoma metastasis

PubMed Central

Boutaud, Olivier; Sosa, I. Romina; Amin, Taneem; Oram, Denise; Adler, David; Hwang, Hyun S.; Crews, Brenda C.; Milne, Ginger; Harris, Bradford K.; Hoeksema, Megan; Knollmann, Bjorn C.; Lammers, Philip E.; Marnett, Lawrence J.; Massion, Pierre P.; Oates, John A.

2016-01-01

Meta-analyses have demonstrated that low dose aspirin reduces the risk of developing adenocarcinoma metastasis, and when colon cancer is detected during aspirin treatment, there is a remarkable 83% reduction in risk of metastasis. As platelets participate in the metastatic process, the anti-platelet action of low dose aspirin likely contributes to its anti-metastatic effect. Cycloxooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) also contributes to metastasis, and we addressed the hypothesis that low dose aspirin also inhibits PGE2 biosynthesis. We show that low dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers (p <0.0001). Aspirin is found to be more potent in colon adenocarcinoma cells than in the platelet, and in lung adenocarcinoma cells its inhibition is equivalent to that in the platelet. Inhibition of COX by aspirin in colon cancer cells is in the context of the metastasis of colon cancer primarily to the liver, the organ exposed to the same high concentrations of aspirin as the platelet. We find that the interaction of activated platelets with lung adenocarcinoma cells up-regulates COX-2 expression and PGE2 biosynthesis, and inhibition of platelet COX-1 by aspirin inhibits PGE2 production by the platelet-tumor cell aggregates. In conclusion, low dose aspirin has a significant effect on extraplatelet cyclooxygenase, and potently inhibits COX-2 in lung and colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of metastasis from adenocarcinomas, and particularly from colon adenocarcinomas, by low dose aspirin results from its effect on platelet COX-1 combined with inhibition of PGE2 biosynthesis in metastasizing tumor cells. PMID:27554763

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PubMed

Shaker, S B; Dirksen, A; Laursen, L C; Maltbaek, N; Christensen, L; Sander, U; Seersholm, N; Skovgaard, L T; Nielsen, L; Kok-Jensen, A

2004-07-01

To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations

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

Matsui, S., E-mail: smatsui@gpi.ac.jp; Mori, Y.; Nonaka, T.

2016-05-15

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films andmore » Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.« less

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations.

PubMed

Matsui, S; Mori, Y; Nonaka, T; Hattori, T; Kasamatsu, Y; Haraguchi, D; Watanabe, Y; Uchiyama, K; Ishikawa, M

2016-05-01

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films and Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study.

PubMed

Torino, Claudia; Gargani, Luna; Sicari, Rosa; Letachowicz, Krzysztof; Ekart, Robert; Fliser, Danilo; Covic, Adrian; Siamopoulos, Kostas; Stavroulopoulos, Aristeidis; Massy, Ziad A; Fiaccadori, Enrico; Caiazza, Alberto; Bachelet, Thomas; Slotki, Itzchak; Martinez-Castelao, Alberto; Coudert-Krier, Marie-Jeanne; Rossignol, Patrick; Gueler, Faikah; Hannedouche, Thierry; Panichi, Vincenzo; Wiecek, Andrzej; Pontoriero, Giuseppe; Sarafidis, Pantelis; Klinger, Marian; Hojs, Radovan; Seiler-Mussler, Sarah; Lizzi, Fabio; Siriopol, Dimitrie; Balafa, Olga; Shavit, Linda; Tripepi, Rocco; Mallamaci, Francesca; Tripepi, Giovanni; Picano, Eugenio; London, Gérard Michel; Zoccali, Carmine

2016-11-07

Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis. Copyright © 2016 by the American Society of Nephrology.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study

PubMed Central

Torino, Claudia; Gargani, Luna; Sicari, Rosa; Letachowicz, Krzysztof; Ekart, Robert; Fliser, Danilo; Covic, Adrian; Siamopoulos, Kostas; Stavroulopoulos, Aristeidis; Massy, Ziad A.; Fiaccadori, Enrico; Caiazza, Alberto; Bachelet, Thomas; Slotki, Itzchak; Martinez-Castelao, Alberto; Coudert-Krier, Marie-Jeanne; Rossignol, Patrick; Gueler, Faikah; Hannedouche, Thierry; Panichi, Vincenzo; Wiecek, Andrzej; Pontoriero, Giuseppe; Sarafidis, Pantelis; Klinger, Marian; Hojs, Radovan; Seiler-Mussler, Sarah; Lizzi, Fabio; Siriopol, Dimitrie; Balafa, Olga; Shavit, Linda; Tripepi, Rocco; Mallamaci, Francesca; Tripepi, Giovanni; Picano, Eugenio; London, Gérard Michel

2016-01-01

Background and objectives Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. Design, setting, participants, & measurements In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound–guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre– and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Results Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Conclusions Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis. PMID:27660305

Application of the LDM algorithm to identify small lung nodules on low-dose MSCT scans

NASA Astrophysics Data System (ADS)

Zhao, Binsheng; Ginsberg, Michelle S.; Lefkowitz, Robert A.; Jiang, Li; Cooper, Cathleen; Schwartz, Lawrence H.

2004-05-01

In this work, we present a computer-aided detection (CAD) algorithm for small lung nodules on low-dose MSCT images. With this technique, identification of potential lung nodules is carried out with a local density maximum (LDM) algorithm, followed by reduction of false positives from the nodule candidates using task-specific 2-D/3-D features along with a knowledge-based nodule inclusion/exclusion strategy. Twenty-eight MSCT scans (40/80mAs, 120kVp, 5mm collimation/2.5mm reconstruction) from our lung cancer screening program that included at least one lung nodule were selected for this study. Two radiologists independently interpreted these cases. Subsequently, a consensus reading by both radiologists and CAD was generated to define a "gold standard". In total, 165 nodules were considered as the "gold standard" (average: 5.9 nodules/case; range: 1-22 nodules/case). The two radiologists detected 146 nodules (88.5%) and CAD detected 100 nodules (60.6%) with 8.7 false-positives/case. CAD detected an additional 19 nodules (6 nodules > 3mm and 13 nodules < 3mm) that had been missed by both radiologists. Preliminary results show that the CAD is capable of detecting small lung nodules with acceptable number of false-positives on low-dose MSCT scans and it can detect nodules that are otherwise missed by radiologists, though a majority are small nodules (< 3mm).

[China National Lung Cancer Screening Guideline with Low-dose Computed 
Tomography (2018 version)].

PubMed

Zhou, Qinghua; Fan, Yaguang; Wang, Ying; Qiao, Youlin; Wang, Guiqi; Huang, Yunchao; Wang, Xinyun; Wu, Ning; Zhang, Guozheng; Zheng, Xiangpeng; Bu, Hong; Li, Yin; Wei, Sen; Chen, Liang'an; Hu, Chengping; Shi, Yuankai; Sun, Yan

2018-02-20

Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice. The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PubMed

Dugernier, Jonathan; Hesse, Michel; Vanbever, Rita; Depoortere, Virginie; Roeseler, Jean; Michotte, Jean-Bernard; Laterre, Pierre-François; Jamar, François; Reychler, Gregory

2017-02-01

To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m ( 99m Tc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99m Tc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Cost-effectiveness of CT screening in the National Lung Screening Trial.

PubMed

Black, William C; Gareen, Ilana F; Soneji, Samir S; Sicks, JoRean D; Keeler, Emmett B; Aberle, Denise R; Naeim, Arash; Church, Timothy R; Silvestri, Gerard A; Gorelick, Jeremy; Gatsonis, Constantine

2014-11-06

The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST. We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions. As compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses. We estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

PubMed

Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

2011-11-01

The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets.

PubMed

Liu, C; Wang, X D; Bronson, R T; Smith, D E; Krinsky, N I; Russell, R M

2000-12-01

There remains a remarkable discordance between the results of observational epidemiological studies and intervention trials using beta-carotene as a potential chemopreventive agent. One question that needs to be examined is whether the adverse outcomes of human beta-carotene trials are related to the large doses of beta-carotene that were administered. In the present study, ferrets were given a physiological (low) dose or a pharmacological (high) dose of beta-carotene supplementation (0.43 mg versus 2.4 mg/kg body wt/day, which is equivalent to 6 mg versus 30 mg/day in humans) and exposed to cigarette smoke for 6 months. We investigated the effects of these doses of beta-carotene on retinoid concentrations, expression of retinoic acid receptors (RARs), activator protein 1 (AP-1; c-Jun and c-Fos), cyclin D1, proliferating cellular nuclear antigen (PCNA), and histopathological changes in the lungs of both normal and cigarette smoke-exposed ferrets. Thirty-six male ferrets were treated in six groups-control, smoke-exposed (SM), low-dose beta-carotene (LBC), high-dose beta-carotene (HBC), low-dose beta-carotene plus smoke exposure (LBC+SM) or high-dose beta-carotene plus smoke exposure (HBC+SM)-for 6 months. Retinoic acid concentration and RAR beta gene expression, but not expression of RAR alpha and RAR gamma, was reduced in the lung tissue of HBC+SM, HBC, SM and LBC+SM ferrets, but not in that of LBC ferrets, as compared with the control group. Expression of AP-1 and PCNA was greater in HBC+SM, HBC, SM and LBC+SM ferrets, but not in the LBC ferrets, as compared with the control group. Increased amounts of cyclin D1 and keratinized squamous metaplasia were observed in the lung tissue of HBC+SM, HBC and SM groups but not in that of the LBC+SM, LBC or control groups. These data suggest that, in contrast with a pharmacological dose of beta-carotene, a physiological dose of beta-carotene in smoke-exposed ferrets has no potentially detrimental effects and may afford weak protection against lung damage induced by cigarette smoke.

Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice.

PubMed

Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Han, Jin-Young; Kim, Bumseok; Lee, Kyuhong

2018-01-01

Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl 2 ), and PHMG + CdCl 2 . Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl 2 group. In contrast, mice in the CdCl 2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl 2 . Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.

Effect of compound Maqin decoction on TGF-β1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

PubMed

Xie, Y H; Li, X P; Xu, Z X; Qian, P; Li, X L; Wang, Y Q

2016-09-02

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-β1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-β1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-β1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Dosimetric comparison of helical tomotherapy, RapidArc, and a novel IMRT & Arc technique for esophageal carcinoma.

PubMed

Martin, Spencer; Chen, Jeff Z; Rashid Dar, A; Yartsev, Slav

2011-12-01

To compare radiotherapy treatment plans for mid- and distal-esophageal cancer with primary involvement of the gastroesophageal (GE) junction using a novel IMRT & Arc technique (IMRT & Arc), helical tomotherapy (HT), and RapidArc (RA1 and RA2). Eight patients treated on HT for locally advanced esophageal cancer with radical intent were re-planned for RA and IMRT&Arc. RA plans employed single and double arcs (RA1 and RA2, respectively), while IMRT&Arc plans had four fixed-gantry IMRT fields and a conformal arc. Dose-volume histogram statistics, dose uniformity, and dose homogeneity were analyzed to compare treatment plans. RA2 plans showed significant improvement over RA1 plans in terms of OAR dose and PTV dose uniformity and homogeneity. HT plan provided best dose uniformity (p=0.001) and dose homogeneity (p=0.002) to planning target volume (PTV), while IMRT&Arc and RA2 plans gave lowest dose to lungs among four radiotherapy techniques with acceptable PTV dose coverage. Mean V(10) of the lungs was significantly reduced by the RA2 plans compared to IMRT&Arc (40.3%, p=0.001) and HT (66.2%, p<0.001) techniques. Mean V(15) of the lungs for the RA2 plans also showed significant improvement over the IMRT&Arc (25.2%, p=0.042) and HT (34.8%, p=0.027) techniques. These improvements came at the cost of higher doses to the heart volume compared to HT and IMRT&Arc techniques. Mean lung dose (MLD) for the IMRT&Arc technique (21.2 ± 5.0% of prescription dose) was significantly reduced compared to HT (26.3%, p=0.004), RA1 (23.3%, p=0.028), and RA2 (23.2%, p=0.017) techniques. The IMRT&Arc technique is a good option for treating esophageal cancer with thoracic involvement. It achieved optimal low dose to the lungs and heart with acceptable PTV coverage. HT is a good option for treating esophageal cancer with little thoracic involvement as it achieves superior dose conformality and uniformity. The RA2 technique provided for improved treatment plans using additional arcs with low doses to the lungs at the cost of increased heart dose. Plan quality could still be improved through the use of additional arcs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy.

PubMed

Tabish, Tanveer A; Lin, Liangxu; Ali, Muhammad; Jabeen, Farhat; Ali, Muhammad; Iqbal, Rehana; Horsell, David W; Winyard, Paul G; Zhang, Shaowei

2018-06-06

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg -1 ) and high (15 mg kg -1 ) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin-eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

American Cancer Society Lung Cancer Screening Guidelines

PubMed Central

Wender, Richard; Fontham, Elizabeth T. H.; Barrera, Ermilo; Colditz, Graham A.; Church, Timothy R.; Ettinger, David S.; Etzioni, Ruth; Flowers, Christopher R.; Gazelle, G. Scott; Kelsey, Douglas K.; LaMonte, Samuel J.; Michaelson, James S.; Oeffinger, Kevin C.; Shih, Ya-Chen Tina; Sullivan, Daniel C.; Travis, William; Walter, Louise; Wolf, Andrew M. D.; Brawley, Otis W.; Smith, Robert A.

2013-01-01

Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. PMID:23315954

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

A Theoretical Approach to Selection of a Biologically Active Substance in Ultra-Low Doses for Effective Action on a Biological System.

PubMed

Boldyreva, Liudmila Borisovna

2018-05-01

 An approach is offered to selecting a biologically active substance (BAS) in ultra-low dose for effective action on a biological system (BS). The technique is based on the assumption that BAS in ultra-low doses exerts action on BS by means of spin supercurrent emerging between the spin structure created by BAS, on the one hand, and the spin structure created by BS, on the other hand. According to modern quantum-mechanical concepts, these spin structures may be virtual particles pairs having precessing spin (that is, be essentially spin vortices in the physical vacuum) and created by the quantum entities that BAS and BS consist of. The action is effective provided there is equality of precession frequencies of spins in these spin structures.  In this work, some methods are considered for determining the precession frequencies of spins in virtual particles pairs: (1) determination of energy levels of quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of the virtual particles pair spin, the effect being initiated by action of magnetic vector potential (the spin-flip effect takes place when the varied frequency of the magnetic vector potential equals the precession frequency of the spin); (3) determining the frequencies of photons effectively acting on BS.  It is shown that the effect of BAS in ultra-low doses on BS can be replaced by the effect of a beam of low-intensity photons, if the frequency of photons equals the precession frequency of spin in spin structures created by BS. Consequently, the color of bodies placed near a biological system is able to exert an effective action on the biological system: that is "color therapy" is possible. It is also supposed that the spin-flip effect may be used not only for determining the precession frequency of spin in spin structures created by BS but also for therapeutic action on biological systems. The Faculty of Homeopathy.

Non-Linear Dose-Response Relationships in Biology, Toxicology and Medicine - An International Conference

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

Calabrese, Edward J.; Kostecki, Paul T.

Conference abstract book contains seven sections: Plenary-4 abstracts; Chemical-9 abstracts; Radiation-7 abstracts; Ultra Low Doses and Medicine-6 abstracts; Biomedical-11 abstracts; Risk Assessment-5 abstracts and Poster Sessions-25 abstracts. Each abstract was provided by the author/presenter participating in the conference.

Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides

PubMed Central

Atkinson, Will; Bérard, Philippe; Bingham, Derek; Birchall, Alan; Blanchardon, Eric; Bull, Richard; Guseva Canu, Irina; Challeton-de Vathaire, Cécile; Cockerill, Rupert; Do, Minh T.; Engels, Hilde; Figuerola, Jordi; Foster, Adrian; Holmstock, Luc; Hurtgen, Christian; Laurier, Dominique; Puncher, Matthew; Riddell, Anthony E.; Samson, Eric; Thierry-Chef, Isabelle; Tirmarche, Margot; Vrijheid, Martine; Cardis, Elisabeth

2017-01-01

Background: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles—particularly through inhalation—occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose–response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. Methods: We conducted a case–control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. Results: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)—adjusted for external radiation, socioeconomic status, and smoking—was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (−1.9, 18) for uranium. Conclusions: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors. See video abstract at, http://links.lww.com/EDE/B232. PMID:28520643

Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial.

PubMed

Walter, Joan E; Heuvelmans, Marjolein A; de Jong, Pim A; Vliegenthart, Rozemarijn; van Ooijen, Peter M A; Peters, Robin B; Ten Haaf, Kevin; Yousaf-Khan, Uraujh; van der Aalst, Carlijn M; de Bock, Geertruida H; Mali, Willem; Groen, Harry J M; de Koning, Harry J; Oudkerk, Matthijs

2016-07-01

US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals. Reports of new nodules after baseline screening have been scarce and are inconsistent because of differences in definitions used. We aimed to identify the occurrence of new solid nodules and their probability of being lung cancer at incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON). In the ongoing, multicentre, randomised controlled NELSON trial, between Dec 23, 2003, and July 6, 2006, 15 822 participants who had smoked at least 15 cigarettes a day for more than 25 years or ten cigarettes a day for more than 30 years and were current smokers, or had quit smoking less than 10 years ago, were enrolled and randomly assigned to receive either screening with low-dose CT (n=7915) or no screening (n=7907). From Jan 28, 2004, to Dec 18, 2006, 7557 individuals underwent baseline screening with low-dose CT; 7295 participants underwent second and third screening rounds. We included all participants with solid non-calcified nodules, registered by the NELSON radiologists as new or smaller than 15 mm(3) (study detection limit) at previous screens. Nodule volume was generated semiautomatically by software. We calculated the maximum volume doubling time for nodules with an estimated percentage volume change of 25% or more, representing the minimum growth rate for the time since the previous scan. Lung cancer diagnosis was based on histology, and benignity was based on histology or stable size for at least 2 years. The NELSON trial is registered at trialregister.nl, number ISRCTN63545820. We analysed data for participants with at least one solid non-calcified nodule at the second or third screening round. In the two incidence screening rounds, the NELSON radiologists registered 1222 new solid nodules in 787 (11%) participants. A new solid nodule was lung cancer in 49 (6%) participants with new solid nodules and, in total, 50 lung cancers were found, representing 4% of all new solid nodules. 34 (68%) lung cancers were diagnosed at stage I. Nodule volume had a high discriminatory power (area under the receiver operating curve 0·795 [95% CI 0·728-0·862]; p<0·0001). Nodules smaller than 27 mm(3) had a low probability of lung cancer (two [0·5%] of 417 nodules; lung cancer probability 0·5% [95% CI 0·0-1·9]), nodules with a volume of 27 mm(3) up to 206 mm(3) had an intermediate probability (17 [3·1%] of 542 nodules; lung cancer probability 3·1% [1·9-5·0]), and nodules of 206 mm(3) or greater had a high probability (29 [16·9%] of 172 nodules; lung cancer probability 16·9% [12·0-23·2]). A volume cutoff value of 27 mm(3) or greater had more than 95% sensitivity for lung cancer. Our study shows that new solid nodules are detected at each screening round in 5-7% of individuals who undergo screening for lung cancer with low-dose CT. These new nodules have a high probability of malignancy even at a small size. These findings should be considered in future screening guidelines, and new solid nodules should be followed up more aggressively than nodules detected at baseline screening. Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds Kankerbestrijding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth

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

Chen, You-Shuang; Peng, Yin-Bo; Yao, Min

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model.more » We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm{sup 2}) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.« less

Investigation of ultra low-dose scans in the context of quantum-counting clinical CT

NASA Astrophysics Data System (ADS)

Weidinger, T.; Buzug, T. M.; Flohr, T.; Fung, G. S. K.; Kappler, S.; Stierstorfer, K.; Tsui, B. M. W.

2012-03-01

In clinical computed tomography (CT), images from patient examinations taken with conventional scanners exhibit noise characteristics governed by electronics noise, when scanning strongly attenuating obese patients or with an ultra-low X-ray dose. Unlike CT systems based on energy integrating detectors, a system with a quantum counting detector does not suffer from this drawback. Instead, the noise from the electronics mainly affects the spectral resolution of these detectors. Therefore, it does not contribute to the image noise in spectrally non-resolved CT images. This promises improved image quality due to image noise reduction in scans obtained from clinical CT examinations with lowest X-ray tube currents or obese patients. To quantify the benefits of quantum counting detectors in clinical CT we have carried out an extensive simulation study of the complete scanning and reconstruction process for both kinds of detectors. The simulation chain encompasses modeling of the X-ray source, beam attenuation in the patient, and calculation of the detector response. Moreover, in each case the subsequent image preprocessing and reconstruction is modeled as well. The simulation-based, theoretical evaluation is validated by experiments with a novel prototype quantum counting system and a Siemens Definition Flash scanner with a conventional energy integrating CT detector. We demonstrate and quantify the improvement from image noise reduction achievable with quantum counting techniques in CT examinations with ultra-low X-ray dose and strong attenuation.

Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

PubMed

Harada, Tasuku; Momoeda, Mikio

2016-12-01

To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. Placebo-controlled, double-blind, randomized trial. Clinical trial sites. Two hundred fifteen subjects with dysmenorrhea. Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. NCT01129102. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Uncertainties in planned dose due to the limited voxel size of the planning CT when treating lung tumors with proton therapy

NASA Astrophysics Data System (ADS)

España, Samuel; Paganetti, Harald

2011-07-01

Dose calculation for lung tumors can be challenging due to the low density and the fine structure of the geometry. The latter is not fully considered in the CT image resolution used in treatment planning causing the prediction of a more homogeneous tissue distribution. In proton therapy, this could result in predicting an unrealistically sharp distal dose falloff, i.e. an underestimation of the distal dose falloff degradation. The goal of this work was the quantification of such effects. Two computational phantoms resembling a two-dimensional heterogeneous random lung geometry and a swine lung were considered applying a variety of voxel sizes for dose calculation. Monte Carlo simulations were used to compare the dose distributions predicted with the voxel size typically used for the treatment planning procedure with those expected to be delivered using the finest resolution. The results show, for example, distal falloff position differences of up to 4 mm between planned and expected dose at the 90% level for the heterogeneous random lung (assuming treatment plan on a 2 × 2 × 2.5 mm3 grid). For the swine lung, differences of up to 38 mm were seen when airways are present in the beam path when the treatment plan was done on a 0.8 × 0.8 × 2.4 mm3 grid. The two-dimensional heterogeneous random lung phantom apparently does not describe the impact of the geometry adequately because of the lack of heterogeneities in the axial direction. The differences observed in the swine lung between planned and expected dose are presumably due to the poor axial resolution of the CT images used in clinical routine. In conclusion, when assigning margins for treatment planning for lung cancer, proton range uncertainties due to the heterogeneous lung geometry and CT image resolution need to be considered.

[CT-Screening for Lung Cancer - what is the Evidence?

PubMed

Watermann, Iris; Reck, Martin

2018-04-01

In patients with lung cancer treatment opportunities and prognosis are correlated to the stage of disease with a chance for curative treatment in patients with early stage disease. Therefore, early detection of lung cancer is of paramount importance for improving the prognosis of lung cancer patients.The National Lung Screening Trial (NLST) has already shown that low-dose CT increases the number of identified early stage lung cancer patients and reduces lung cancer related mortality. Critically considered in terms of CT-screening are false-positive results, overdiagnosis and unessential invasive clarification. Preliminary results of relatively small European trials haven´t yet confirmed the results of the NLST-study.Until now Lung Cancer Screening by low dose CT-scan or other methods is neither approved nor available in Germany.To improve the efficacy of CT-Screening and to introduce early detection of lung cancer in standard practice, additional, complementing methods should be further evaluated. One option might be the supplementary analysis of biomarkers in liquid biopsies or exhaled breath condensates. In addition, defining the high-risk population is of great relevance to identify candidates who might benefit of early detection programs. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

NASA Astrophysics Data System (ADS)

Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J.

2013-10-01

Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons (<10 MV) and larger fields (>5 × 5 cm2) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ˜1 cm). For the phantom, square fields of 1 × 1 cm2, 3 × 3 cm2, or 5 × 5 cm2 were applied. However, in the patient, 3 × 1 cm2, 3 × 2 cm2, 3 × 2.5 cm2, or 3 × 3 cm2 field sizes were used in simulations to assure target coverage in the superior-inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was generated by considering the extent of tumour motion over the patient's breathing cycle and set-up uncertainties. All patient dose results were normalized such that at least 95% of the PTV received at least 54 Gy (i.e. D95 = 54 Gy). Further, we introduce ‘LED maps’ as a novel clinical tool to compare the magnitude of LED resulting from the various SBRT arc plans. Results from the phantom simulation suggest that the best lung sparing occurred for RT parameters that cause severe LED. For equal tumour dose coverage, normal lung dose (2 cm outside the target region) was reduced from 92% to 23%, comparing results between the 18 MV (5 × 5 cm2) and 18 MV (1 × 1 cm2) arc simulations. In addition to reduced lung dose for the 18 MV (1 × 1 cm2) arc, maximal tumour dose increased beyond 125%. Thus, LED can create steep dose gradients to spare normal lung, while increasing tumour dose levels (if desired). In the patient simulation, a LED-optimized arc plan was designed using either 18 MV (3 × 1 cm2) or 6 MV (3 × 3cm2) beams. Both plans met the D95 dose coverage requirement for the target. However, the LED-optimized plan increased the maximum, mean, and minimum dose within the PTV by as much as 80 Gy, 11 Gy, and 3 Gy, respectively. Despite increased tumour dose levels, the 18 MV (3 × 1 cm2) arc plan improved or maintained the V20, V5, and mean lung dose metrics compared to the 6 MV (3 × 3 cm2) simulation. We conclude that LED-SBRT has the potential to increase dose gradients, and dose levels within a small lung tumour. The magnitude of tumour dose increase or lung sparing can be optimized through manipulation of RT parameters (e.g. beam energy and field size).

Comparison of sensitivity of lung nodule detection between radiologists and technologists on low-dose CT lung cancer screening images

PubMed Central

Kakinuma, R; Ashizawa, K; Kobayashi, T; Fukushima, A; Hayashi, H; Kondo, T; Machida, M; Matsusako, M; Minami, K; Oikado, K; Okuda, M; Takamatsu, S; Sugawara, M; Gomi, S; Muramatsu, Y; Hanai, K; Muramatsu, Y; Kaneko, M; Tsuchiya, R; Moriyama, N

2012-01-01

Objectives The objective of this study was to compare the sensitivity of detection of lung nodules on low-dose screening CT images between radiologists and technologists. Methods 11 radiologists and 10 technologists read the low-dose screening CT images of 78 subjects. On images with a slice thickness of 5 mm, there were 60 lung nodules that were ≥5 mm in diameter: 26 nodules with pure ground-glass opacity (GGO), 7 nodules with mixed ground-glass opacity (GGO with a solid component) and 27 solid nodules. On images with a slice thickness of 2 mm, 69 lung nodules were ≥5 mm in diameter: 35 pure GGOs, 7 mixed GGOs and 27 solid nodules. The 21 observers read screening CT images of 5-mm slice thickness at first; then, 6 months later, they read screening CT images of 2-mm slice thickness from the 78 subjects. Results The differences in the mean sensitivities of detection of the pure GGOs, mixed GGOs and solid nodules between radiologists and technologists were not statistically significant, except for the case of solid nodules; the p-values of the differences for pure GGOs, mixed GGOs and solid nodules on the CT images with 5-mm slice thickness were 0.095, 0.461 and 0.005, respectively, and the corresponding p-values on CT images of 2-mm slice thickness were 0.971, 0.722 and 0.0037, respectively. Conclusion Well-trained technologists may contribute to the detection of pure and mixed GGOs ≥5 mm in diameter on low-dose screening CT images. PMID:22919013

Cell-type specificity of lung cancer associated with low-dose soil heavy metal contamination in Taiwan: An ecological study

PubMed Central

2013-01-01

Background Numerous studies have examined the association between heavy metal contamination (including arsenic [As], cadmium [Cd], chromium [Cr], copper [Cu], mercury [Hg], nickel [Ni], lead [Pb], and zinc [Zn]) and lung cancer. However, data from previous studies on pathological cell types are limited, particularly regarding exposure to low-dose soil heavy metal contamination. The purpose of this study was to explore the association between soil heavy metal contamination and lung cancer incidence by specific cell type in Taiwan. Methods We conducted an ecological study and calculated the annual averages of eight soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) by using data from the Taiwan Environmental Protection Administration from1982 to 1986. The age-standardized incidence rates of lung cancer according to two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]) were obtained from the National Cancer Registry Program conducted in Taiwan from 2001 to 2005. A geographical information system was used to plot the maps of soil heavy metal concentration and lung cancer incidence rates. Poisson regression models were used to obtain the adjusted relative ratios (RR) and 95% confidence intervals (CI) for the lung cancer incidence associated with soil heavy metals. Results For males, the trend test for lung SCC incidence caused by exposure to Cr, Cu, Hg, Ni, and Zn showed a statistically significant dose–response relationship. However, for lung AC, only Cu and Ni had a significant dose–response relationship. As for females, those achieving a statistically significant dose–response relationship for the trend test were Cr (P = 0.02), Ni (P = 0.02), and Zn (P= 0.02) for lung SCC, and Cu (P < 0.01) and Zn (P = 0.02) for lung AC. Conclusion The current study suggests that a dose–response relationship exists between low-dose soil heavy metal concentration and lung cancer occurrence by specific cell-type; however, the relevant mechanism should be explored further. PMID:23575356

Multifactorial Analysis of Mortality in Screening Detected Lung Cancer.

PubMed

Digumarthy, Subba R; De Man, Ruben; Canellas, Rodrigo; Otrakji, Alexi; Wang, Ge; Kalra, Mannudeep K

2018-01-01

We hypothesized that severity of coronary artery calcification (CAC), emphysema, muscle mass, and fat attenuation can help predict mortality in patients with lung cancer participating in the National Lung Screening Trial (NLST). Following regulatory approval from the Cancer Data Access System (CDAS), all patients diagnosed with lung cancer at the time of the screening study were identified. These subjects were classified into two groups: survivors and nonsurvivors at the conclusion of the NLST trial. These groups were matched based on their age, gender, body mass index (BMI), smoking history, lung cancer stage, and survival time. CAC, emphysema, muscle mass, and subcutaneous fat attenuation were quantified on baseline low-dose chest CT (LDCT) for all patients in both groups. Nonsurvivor group had significantly greater CAC, decreased muscle mass, and higher fat attenuation compared to the survivor group ( p < 0.01). No significant difference in severity of emphysema was noted between the two groups ( p > 0.1). We thus conclude that it is possible to create a quantitative prediction model for lung cancer mortality for subjects with lung cancer detected on screening low-dose CT (LDCT).

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

PubMed

Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

2016-01-01

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Dosimetric comparison of normal structures associated with accelerated partial breast irradiation and whole breast irradiation delivered by intensity modulated radiotherapy for early breast cancer after breast conserving surgery.

PubMed

Wu, S; He, Z; Guo, J; Li, F; Lin, Q; Guan, X

2014-01-01

To assess the heart and lung dosimetry results associated with accelerated partial breast irradiation intensity-modulated radiotherapy (APBI-IMRT) and whole breast field-in-field intensity-modulated radiotherapy (WBI-FIF-IMRT). A total of 29 patients with early-stage breast cancer after lumpectomy were included in this study. APBI-IMRT and WBI-FIF-IMRT plans were generated for each patient. The dosimetric parameters of ipsilateral lung and heart in both plans were then compared with and without radiobiological correction. With and without radiobiological correction, the volume of ipsilateral lung showed a substantially lower radiation exposure in APBI-IMRT with moderate to high doses (P < 0.05) but non-significant increases in volume of ipsilateral lung in 2.5 Gy than WBI-FIF-IMRT (P > 0.905).There was no significant difference in volume of ipsilateral lung receiving 1, 2.5, and 5 Gy between APBI-IMRT and WBI (P > 0.05) in patients with medial tumor location, although APBI-IMRT exposed more lung to 2.5 and 5 Gy. APBI-IMRT significantly decreases the volume of heart receiving low to high doses in left-sided breast cancer (P < 0.05). APBI-IMRT can significantly spare the volume of heart and ipsilateral lung receiving moderate and high dose. Non-significant increases in volume of the ipsilateral lung exposed to low doses of radiation were observed for APBI-IMRT in comparison to WBI-FIF-IMRT, particularly in patients with medial tumor location. With the increasing interest in APBI-IMRT, our data may help clinicians individualize patient treatment decisions.

SU-E-T-283: Dose Perturbations Near Heterogeneity Junctions for Modulated-Scanning Protons

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

Deng, Y; Li, Y; Sheng, Y

2015-06-15

Purpose: To compare calculated and measured doses near heterogeneity junctions of tissue-substitute materials for modulated-scanning protons. Methods: Three heterogeneous phantoms were configured using slabs of various plastics to simulate lung, fat, soft-tissue (polystyrene), and bone with known relative linear stopping powers (RLSPs). Each phantom consisted of soft-tissue and a single heterogeneity of a 5 or 10 cm thickness of a non-soft-tissue material. CT images were loaded into a Syngo treatment planning system and each material contoured and assigned its RLSP. Planning target volumes (PTVs) were drawn such that a beam would partially traverse the heterogeneity and partially only soft-tissue. Lateralmore » profiles were measured using EDR2 films at a minimum of six depths between the phantom surface and the depth corresponding to the beam range. Absolute doses were measured inside and distal to the PTV in all phantoms using either a parallel plate or thimble chamber. Additional dose measurements were made between two lung slabs. Results: Profiles measured by film generally agreed with calculations except for depths distal to lung and fat junctions. Measured lateral penumbras for depths at the distal junction of lung were found to be wider than calculated ones. Compared with calculated doses, measured doses in the PTVs were 5.19% and 2.51% lower for lung and fat respectively but for bone were 0.2% higher. Measured doses for depths distal to the PTV were up to 29.65% and 10.58% higher for lung and fat, respectively but 6.30% lower for bone. Conclusion: The low measured doses in the PTVs for lung and fat might be due to underestimation of lateral scattering of protons. The higher measured doses distal to the PTV for the lung and fat are a Result of a shortened calculated beam range whereas the higher dose distal to the bone junction is within uncertainties.« less

ESR/ERS white paper on lung cancer screening

PubMed Central

Bonomo, Lorenzo; Gaga, Mina; Nackaerts, Kristiaan; Peled, Nir; Prokop, Mathias; Remy-Jardin, Martine; von Stackelberg, Oyunbileg; Sculier, Jean-Paul

2015-01-01

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged. PMID:25929956

Emphysema quantification and lung volumetry in chest X-ray equivalent ultralow dose CT - Intra-individual comparison with standard dose CT.

PubMed

Messerli, Michael; Ottilinger, Thorsten; Warschkow, René; Leschka, Sebastian; Alkadhi, Hatem; Wildermuth, Simon; Bauer, Ralf W

2017-06-01

To determine whether ultralow dose chest CT with tin filtration can be used for emphysema quantification and lung volumetry and to assess differences in emphysema measurements and lung volume between standard dose and ultralow dose CT scans using advanced modeled iterative reconstruction (ADMIRE). 84 consecutive patients from a prospective, IRB-approved single-center study were included and underwent clinically indicated standard dose chest CT (1.7±0.6mSv) and additional single-energy ultralow dose CT (0.14±0.01mSv) at 100kV and fixed tube current at 70mAs with tin filtration in the same session. Forty of the 84 patients (48%) had no emphysema, 44 (52%) had emphysema. One radiologist performed fully automated software-based pulmonary emphysema quantification and lung volumetry of standard and ultralow dose CT with different levels of ADMIRE. Friedman test and Wilcoxon rank sum test were used for multiple comparison of emphysema and lung volume. Lung volumes were compared using the concordance correlation coefficient. The median low-attenuation areas (LAA) using filtered back projection (FBP) in standard dose was 4.4% and decreased to 2.6%, 2.1% and 1.8% using ADMIRE 3, 4, and 5, respectively. The median values of LAA in ultralow dose CT were 5.7%, 4.1% and 2.4% for ADMIRE 3, 4, and 5, respectively. There was no statistically significant difference between LAA in standard dose CT using FBP and ultralow dose using ADMIRE 4 (p=0.358) as well as in standard dose CT using ADMIRE 3 and ultralow dose using ADMIRE 5 (p=0.966). In comparison with standard dose FBP the concordance correlation coefficients of lung volumetry were 1.000, 0.999, and 0.999 for ADMIRE 3, 4, and 5 in standard dose, and 0.972 for ADMIRE 3, 4 and 5 in ultralow dose CT. Ultralow dose CT at chest X-ray equivalent dose levels allows for lung volumetry as well as detection and quantification of emphysema. However, longitudinal emphysema analyses should be performed with the same scan protocol and reconstruction algorithms for reproducibility. Copyright © 2017 Elsevier B.V. All rights reserved.

Intensity-modulated radiotherapy for locally advanced non-small-cell lung cancer: a dose-escalation planning study.

PubMed

Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

2011-05-01

To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Xu, Q; Han, H; Xing, L

Purpose: Dictionary learning based method has attracted more and more attentions in low-dose CT due to the superior performance on suppressing noise and preserving structural details. Considering the structures and noise vary from region to region in one imaging object, we propose a region-specific dictionary learning method to improve the low-dose CT reconstruction. Methods: A set of normal-dose images was used for dictionary learning. Segmentations were performed on these images, so that the training patch sets corresponding to different regions can be extracted out. After that, region-specific dictionaries were learned from these training sets. For the low-dose CT reconstruction, amore » conventional reconstruction, such as filtered back-projection (FBP), was performed firstly, and then segmentation was followed to segment the image into different regions. Sparsity constraints of each region based on its dictionary were used as regularization terms. The regularization parameters were selected adaptively according to different regions. A low-dose human thorax dataset was used to evaluate the proposed method. The single dictionary based method was performed for comparison. Results: Since the lung region is very different from the other part of thorax, two dictionaries corresponding to lung region and the rest part of thorax respectively were learned to better express the structural details and avoid artifacts. With only one dictionary some artifact appeared in the body region caused by the spot atoms corresponding to the structures in the lung region. And also some structure in the lung regions cannot be recovered well by only one dictionary. The quantitative indices of the result by the proposed method were also improved a little compared to the single dictionary based method. Conclusion: Region-specific dictionary can make the dictionary more adaptive to different region characteristics, which is much desirable for enhancing the performance of dictionary learning based method.« less

Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

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

Yu, Victoria; Kishan, Amar U.; Cao, Minsong

2014-03-15

Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Basedmore » on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.« less

Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

NASA Astrophysics Data System (ADS)

Buldakov, M. A.; Tretyakova, M. S.; Ryabov, V. B.; Klimov, I. A.; Kutenkov, O. P.; Kzhyshkowska, J.; Bol'shakov, M. A.; Rostov, V. V.; Cherdyntseva, N. V.

2017-05-01

To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. “Sinus-150” was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation.

Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose.

PubMed

Ung, Keith T; Rao, Nagaraja; Weers, Jeffry G; Huang, Daniel; Chan, Hak-Kim

2016-09-25

Inhaled drugs all too often deliver only a fraction of the emitted dose to the target lung site due to deposition in the extrathoracic region (i.e., mouth and throat), which can lead to increased variation in lung exposure, and in some instances increases in local and systemic side effects. For aerosol medications, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, rugosity) to minimize deposition in the mouth-throat and maximize the total lung dose. This study evaluated a co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations of insulin microparticles. The binary co-solvent system studied included water as the primary solvent mixed with an organic co-solvent, e.g., ethanol. Factors such as the relative rate of evaporation of each component of a binary co-solvent mixture, and insulin solubility in each component were considered in selecting feedstock compositions. A water-ethanol co-solvent mixture with a composition range considered suitable for modulating particle shell formation during drying was selected for experimental investigation. An Alberta Idealized Throat model was used to evaluate the in vitro total lung dose of a series of spray dried insulin formulations engineered with different bulk powder properties and delivered with two prototype inhalers that fluidize and disperse powder using different principles. The in vitro total lung dose of insulin microparticles was improved and favored for powders with low bulk density and small primary particle size, with reduction of deposition in the extrathoracic region. The results demonstrated that a total lung dose >95% of the delivered dose can be achieved with engineered particles, indicating a high degree of lung targeting, almost completely bypassing deposition in the mouth-throat. Copyright © 2016 Elsevier B.V. All rights reserved.

American Cancer Society lung cancer screening guidelines.

PubMed

Wender, Richard; Fontham, Elizabeth T H; Barrera, Ermilo; Colditz, Graham A; Church, Timothy R; Ettinger, David S; Etzioni, Ruth; Flowers, Christopher R; Gazelle, G Scott; Kelsey, Douglas K; LaMonte, Samuel J; Michaelson, James S; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Sullivan, Daniel C; Travis, William; Walter, Louise; Wolf, Andrew M D; Brawley, Otis W; Smith, Robert A

2013-01-01

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. Copyright © 2013 American Cancer Society, Inc.

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

Lee, C.K.K.; Bloomfield, C.D.; Goldman, A.I.

Since Hodgkin's disease patients with large mediastinal masses frequently relapse in the intrathoracic area after regular mantle field irradiation, the feasibility and utility of low dose lung irradiation as an initial part of the supradiaphragmatic field was examined. Fifteen newly diagnosed patients with Hodgkin's disease and large mediastinal masses were treated with 1000 to 2000 rad to the lung as a part of extended field radiotherapy. All patients received radiotherapy alone. Results of treatment were compared with those in 20 similar patients who were treated only with extended field irradiation. With a minimum follow-up of 24 months, only 2 patientsmore » (13%) who received lung irradiation have recurred and only one of these recurred in the lung. In contrast 15 (79%) of the 19 complete responders who were treated without lung irradiation had relapsed by 24 months, 9 in the intrathoracic region. Recurrence-free survival was significantly longer in patients who received lung irradiation. No increased frequency in serious complications has been experienced to date with low dose whole lung irradiation, compared with regular mantle field treatment. This study suggests that lung irradiation may be a feasible alternative to adjuvant combination chemotherapy when treating patients with Hodgkin's desease and large mediastinal masses.« less

Ultra-Low-Dropout Linear Regulator

NASA Technical Reports Server (NTRS)

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2011-01-01

A radiation-tolerant, ultra-low-dropout linear regulator can operate between -150 and 150 C. Prototype components were demonstrated to be performing well after a total ionizing dose of 1 Mrad (Si). Unlike existing components, the linear regulator developed during this activity is unconditionally stable over all operating regimes without the need for an external compensation capacitor. The absence of an external capacitor reduces overall system mass/volume, increases reliability, and lowers cost. Linear regulators generate a precisely controlled voltage for electronic circuits regardless of fluctuations in the load current that the circuit draws from the regulator.

Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak.

PubMed

Dauber, I M; Pluss, W T; VanGrondelle, A; Trow, R S; Weil, J V

1985-08-01

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.

Dosimetric verification of small fields in the lung using lung-equivalent polymer gel and Monte Carlo simulation.

PubMed

Gharehaghaji, Nahideh; Dadgar, Habib Alah

2018-01-01

The main purpose of this study was evaluate a polymer-gel-dosimeter (PGD) for three-dimensional verification of dose distributions in the lung that is called lung-equivalent gel (LEG) and then to compare its result with Monte Carlo (MC) method. In the present study, to achieve a lung density for PGD, gel is beaten until foam is obtained, and then sodium dodecyl sulfate is added as a surfactant to increase the surface tension of the gel. The foam gel was irradiated with 1 cm × 1 cm field size in the 6 MV photon beams of ONCOR SIEMENS LINAC, along the central axis of the gel. The LEG was then scanned on a 1.5 Tesla magnetic resonance imaging scanner after irradiation using a multiple-spin echo sequence. Least-square fitting the pixel values from 32 consecutive images using a single exponential decay function derived the R2 relaxation rates. Moreover, 6 and 18 MV photon beams of ONCOR SIEMENS LINAC are simulated using MCNPX MC Code. The MC model is used to calculate the depth dose water and low-density water resembling the soft tissue and lung, respectively. Percentages of dose reduction in the lung region relative to homogeneous phantom for 6 MV photon beam were 44.6%, 39%, 13%, and 7% for 0.5 cm × 0.5 cm, 1 cm × 1 cm, 2 cm × 2 cm, and 3 cm × 3 cm fields, respectively. For 18 MV photon beam, the results were found to be 82%, 69%, 46%, and 25.8% for the same field sizes, respectively. Preliminary results show good agreement between depth dose measured with the LEG and the depth dose calculated using MCNP code. Our study showed that the dose reduction with small fields in the lung was very high. Thus, inaccurate prediction of absorbed dose inside the lung and also lung/soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

A model for treating avian aspergillosis: serum and lung tissue kinetics for Japanese quail (Coturnix japonica) following single and multiple aerosol exposures of a nanoparticulate itraconazole suspension.

PubMed

Rundfeldt, Chris; Wyska, Elżbieta; Steckel, Hartwig; Witkowski, Andrzej; Jeżewska-Witkowska, Grażyna; Wlaź, Piotr

2013-11-01

Aspergillosis is frequently reported in parrots, falcons and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but administration requires repeated oral dosing and the safety margin is narrow. We describe lung tissue and serum pharmacokinetics of a nanoparticulate ITRA suspension administered to Japanese quail by aerosol exposure. Aerosolized ITRA (1 and 10% suspension) administered over 30 min did not induce adverse clinical reactions in quail upon single or 5-day repeated doses. High lung concentrations, well above the inhibitory levels for A. fumigatus, of 4.14 ± 0.19 μg/g and 27.5 ± 4.58 μg/g (mean ± SEM, n = 3), were achieved following single-dose inhalation of 1% and 10% suspension, respectively. Upon multiple dose administration of 10% suspension, mean lung concentrations reached 104.9 ± 10.1 μg/g. Drug clearance from the lungs was slow with terminal half-lives of 19.7 h and 35.8 h following inhalation of 1% and 10% suspension, respectively. Data suggest that lung clearance is solubility driven. Lung concentrations of hydroxy-itraconazole reached 1-2% of the ITRA lung tissue concentration indicating metabolism in lung tissue. Steady, but low, serum concentrations of ITRA could be measured after multiple dose administration, reaching less than 0.1% of the lung tissue concentration. This formulation may represent a novel, easy to administer treatment modality for fungal lung infection, preventing high systemic exposure. It may also be useful as metaphylaxis to prevent the outbreak of aspergillosis in colonized animals.

SU-F-BRD-09: Is It Sufficient to Use Only Low Density Tissue-Margin to Compensate Inter-Fractionation Setup Uncertainties in Lung Treatment?

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

Nie, K; Yue, N; Chen, T

2014-06-15

Purpose: In lung radiation treatment, PTV is formed with a margin around GTV (or CTV/ITV). Although GTV is most likely of water equivalent density, the PTV margin may be formed with the surrounding low-density tissues, which may lead to unreal dosimetric plan. This study is to evaluate whether the concern of dose calculation inside the PTV with only low density margin could be justified in lung treatment. Methods: Three SBRT cases were analyzed. The PTV from the original plan (Plan-O) was created with a 5–10 mm margin outside the ITV to incorporate setup errors and all mobility from 10 respiratorymore » phases. Test plans were generated with the GTV shifted to the PTV edge to simulate the extreme situations with maximum setup uncertainties. Two representative positions as the very posterior-superior (Plan-PS) and anterior-inferior (Plan-AI) edge were considered. The virtual GTV was assigned a density of 1.0 g.cm−3 and surrounding lung, including the PTV margin, was defined as 0.25 g.cm−3. Also, additional plan with a 1mm tissue-margin instead of full lung-margin was created to evaluate whether a composite-margin (Plan-Comp) has a better approximation for dose calculation. All plans were generated on the average CT using Analytical Anisotropic Algorithm with heterogeneity correction on and all planning parameters/monitor unites remained unchanged. DVH analyses were performed for comparisons. Results: Despite the non-static dose distribution, the high-dose region synchronized with tumor positions. This might due to scatter conditions as greater doses were absorbed in the solid-tumor than in the surrounding low-density lungtissue. However, it still showed missing target coverage in general. Certain level of composite-margin might give better approximation for the dosecalculation. Conclusion: Our exploratory results suggest that with the lungmargin only, the planning dose of PTV might overestimate the coverage of the target during treatment. The significance of this overestimation might warrant further investigation.« less

A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

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

Palma, Giuseppe; Monti, Serena; D'Avino, Vittoria

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. Themore » coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.« less

Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis

PubMed Central

Callera, Glaucia E.; Antunes, Tayze T.; Correa, Jose W.; Moorman, Danielle; Gutsol, Alexey; He, Ying; Cat, Aurelie Nguyen Dinh; Briones, Ana M.; Montezano, Augusto C.; Burns, Kevin D.; Touyz, Rhian M.

2016-01-01

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes. PMID:27612496

Lung Cancer Screening May Benefit Those at Highest Risk

Cancer.gov

People at the highest risk for lung cancer, based on a risk model, may be more likely to benefit from screening with low-dose CT, a new analysis suggests. The study authors believe the findings may better define who should undergo lung cancer screening, as this Cancer Currents blog post explains.

From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

PubMed

Shay, Jerry W; Cucinotta, Francis A; Sulzman, Frank M; Coleman, C Norman; Minna, John D

2011-11-15

On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation. In contrast, the NCI is endeavoring to estimate the increased lung cancer risk from the potential widespread implementation of computed tomographic (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans from the screening (which uses "low-dose" CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low-dose exposure to Earth's radiation. The workshop examined preclinical models, epidemiology, molecular markers, "omics" technology, radiobiology issues, and lung stem cells that relate to the development of lung cancer. ©2011 AACR

Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study.

PubMed

Ito, Makoto; Shimizu, Hidetoshi; Aoyama, Takahiro; Tachibana, Hiroyuki; Tomita, Natsuo; Makita, Chiyoko; Koide, Yutaro; Kato, Daiki; Ishiguchi, Tsuneo; Kodaira, Takeshi

2018-04-04

Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose. Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes. The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010). The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.

Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

PubMed Central

Bain, William G.; Tripathi, Ashutosh; Mandke, Pooja; Gans, Jonathan H.; D'Alessio, Franco R.; Sidhaye, Venkataramana K.; Aggarwal, Neil R.

2016-01-01

Background. Chronic obstructive pulmonary disease (COPD) is a common, smoking-related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1) and 21% or 35–40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40%) for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35–40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-α and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-α secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low-dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis. PMID:27403445

Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT.

PubMed

Aschenbrenner, Katharina P; Guthier, Christian V; Lyatskaya, Yulia; Boda-Heggemann, Judit; Wenz, Frederik; Hesser, Jürgen W

2017-09-01

In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the patient is negligible. Copyright © 2017. Published by Elsevier GmbH.

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

Brady, S; Shulkin, B

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 withmore » 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-localization of hybrid CT anatomy and PET radioisotope uptake.« less

[Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy].

PubMed

Shen, Wen-bin; Zhu, Shu-chai; Gao, Hong-mei; Li, You-mei; Liu, Zhi-kun; Li, Juan; Su, Jing-wei; Wan, Jun

2013-01-01

To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP. Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria. The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group. The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the effect in predicting radiation pneumonitis.

Submillisievert standard-pitch CT pulmonary angiography with ultra-low dose contrast media administration: A comparison to standard CT imaging.

PubMed

Suntharalingam, Saravanabavaan; Mikat, Christian; Stenzel, Elena; Erfanian, Youssef; Wetter, Axel; Schlosser, Thomas; Forsting, Michael; Nassenstein, Kai

2017-01-01

To evaluate the image quality and radiation dose of submillisievert standard-pitch CT pulmonary angiography (CTPA) with ultra-low dose contrast media administration in comparison to standard CTPA. Hundred patients (56 females, 44 males, mean age 69.6±15.4 years; median BMI: 26.6, IQR: 5.9) with suspected pulmonary embolism were examined with two different protocols (n = 50 each, group A: 80 kVp, ref. mAs 115, 25 ml of contrast medium; group B: 100 kVp, ref. mAs 150, 60 ml of contrast medium) using a dual-source CT equipped with automated exposure control. Objective and subjective image qualities, radiation exposure as well as the frequency of pulmonary embolism were evaluated. There was no significant difference in subjective image quality scores between two groups regarding pulmonary arteries (p = 0.776), whereby the interobserver agreement was excellent (group A: k = 0.9; group B k = 1.0). Objective image analysis revealed that signal intensities (SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the pulmonary arteries were equal or significantly higher in group B. There was no significant difference in the frequency of pulmonary embolism (p = 0.65). Using the low dose and low contrast media protocol resulted in a radiation dose reduction by 71.8% (2.4 vs. 0.7 mSv; p<0.001). This 80 kVp standard pitch CTPA protocol with 25 ml contrast agent volume can obtain sufficient image quality to exclude or diagnose pulmonary emboli while reducing radiation dose by approximately 71%.

Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model

PubMed Central

Tessaro, Irene; Modina, Silvia; Lodde, Valentina; Sivelli, Giulia; Franciosi, Federica; Terzaghi, Laura; Luchini, Patrizia; Rumio, Cristiano; Luciano, Alberto Maria

2017-01-01

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested. Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant. Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05 vs. control group) and reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone treatment). Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment. PMID:29062793

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

PubMed

Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

Dosimetric benefits of automation in the treatment of lower thoracic esophageal cancer: Is manual planning still an alternative option?

PubMed

Li, Xiadong; Wang, Lu; Wang, Jiahao; Han, Xu; Xia, Bing; Wu, Shixiu; Hu, Weigang

2017-01-01

This study aimed to design automated volumetric-modulated arc therapy (VMAT) plans in Pinnacle auto-planning and compare it with manual plans for patients with lower thoracic esophageal cancer (EC). Thirty patients with lower thoracic EC were randomly selected for replanning VMAT plans using auto-planning in Pinnacle treatment planning system (TPS) version 9.10. Historical plans of these patients were then compared. Dose-volume histogram (DVH) statistics, dose uniformity, and dose homogeneity were analyzed to evaluate treatment plans. Auto-planning was superior in terms of conformity index (CI) and homogeneity index (HI) for planning target volume (PTV), significantly improving 8.2% (p = 0.013) and 25% (p = 0.007) compared with manual planning, respectively, and decreasing dose of heart and liver irradiated by 20 to 40 Gy and 5 to 30 Gy, respectively (p < 0.05). Meanwhile, auto-planning further reduced the maximum dose (D max ) of spinal cord by 6.9 Gy compared with manual planning (p = 0.000). Additionally, manual planning showed the significantly lower low-dose volume (V 5 ) for the lung (p = 0.005). For auto-planning, the V 5 of the lung was significantly associated with the relative volume index (the volume ratio of PTV to the lung), and the correlation coefficient (R) and p-value were 0.994 and 0.000. Pinnacle auto-planning achieved superior target conformity and homogeneity and similar target coverage compared with historical manual planning. Most of organs at risk (OARs) sparing was significantly improved by auto-planning except for the V 5 of the lung, and the low dose distribution was highly associated with PTV volume and lung volume in auto-planning. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

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

Oborn, B; Ge, Y; Hardcastle, N

Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: 9 clinical lung plans were recalculated using Monte Carlo methods and external inline (parallel to the beam direction) magnetic fields of 0.5 T, 1.0 T and 3 T were included. Three plans were 6MV 3D-CRT and six were 6MV IMRT. The GTV’s ranged from 0.8 cc to 73 cc, while the PTV ranged from 1 cc to 180 cc. Results: The inline magnetic field has a moderatemore » impact in lung dose distributions by reducing the lateral scatter of secondary electrons and causing a small local dose increase. Superposition of multiple small beams acts to superimpose the small dose increases and can lead to significant dose enhancements, especially when the GTV is low density. Two plans with very small, low mean density GTV’s (<1 cc, ρ(mean)<0.35g/cc) showed uniform increases of 16% and 23% at 1 T throughout the PTV. Three plans with moderate mean density PTV’s (3–13 cc, ρ(mean)=0.58–0.67 g/cc) showed 6% mean dose enhancement at 1 T in the PTV, however not uniform throughout the GTV/PTV. Replanning would benefit these cases. The remaining 5 plans had large dense GTV’s (∼ 1 g/cc) and so only a minimal (<2%) enhancement was seen. In general the mean dose enhancement at 0.5 T was 60% less than 1 T, while 5–50% higher at 3 T. Conclusions: A paradigm shift in the efficacy of small lung tumor radiotherapy is predicted with future inline MRI-linac systems. This will be achieved by carefully taking advantage of the reduction of lateral electronic disequilibrium withing lung tissue that is induced naturally inside strong inline magnetic fields.« less

Comparison of acute proton, photon, and low-dose priming effects on genes associated with extracellular matrix and adhesion molecules in the lungs

PubMed Central

2013-01-01

Background Crew members on space missions inevitably are exposed to low background radiation and can receive much higher doses during solar particle events (SPE) that consist primarily of protons. Ionizing radiation could cause lung pathologies. Cell adhesion molecules (CAM) are believed to participate in fibrogenesis. Interactions between CAM and extracellular matrix (ECM) affect epithelial repair mechanisms in the lung. However, there are very limited data on biological effects of protons on normal lung tissue. Numerous reports have shown that exposure to low-dose/low-dose-rate (LDR) radiation can result in radioadaptation that renders cells more resistant to subsequent acute radiation. The goal of this study was to compare expression of genes associated with ECM and CAM, as well as critical profibrotic mediators, in mouse lungs after acute irradiation with photons and protons, and also determine whether pre-exposure to LDR γ-rays induces an adaptive effect. Results Overall, a marked difference was present in the proton vs. photon groups in gene expression. When compared to 0 Gy, more genes were affected by protons than by photons at both time points (11 vs. 6 on day 21 and 14 vs. 8 on day 56), and all genes affected by protons were upregulated. Many genes were modulated by LDR γ-rays when combined with photons or protons. Col1a1, mmp14, and mmp15 were significantly upregulated by all radiation regimens on day 21. Similarly, the change in expression of profibrotic proteins was also detected after acute and combination irradiation. Conclusion These data show that marked differences were present between acutely delivered protons and photons in modulating genes, and the effect of protons was more profound than that of photons. Pre-exposure to LDR γ-rays ‘normalized’ some genes that were modified by acute irradiation. PMID:23374750

Low-dose lung cancer screening with photon-counting CT: a feasibility study

NASA Astrophysics Data System (ADS)

Symons, Rolf; Cork, Tyler E.; Sahbaee, Pooyan; Fuld, Matthew K.; Kappler, Steffen; Folio, Les R.; Bluemke, David A.; Pourmorteza, Amir

2017-01-01

To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema. The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P  <  0.01), while HUs for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P  <  0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2  ±  0.3 HU versus 15.8  ±  0.2 HU, P  =  0.03 16.1  ±  0.3 HU versus 18.0  ±  0.4 HU, P  =  0.003 and 16.1  ±  0.3 HU versus 17.9  ±  0.3 HU, P  =  0.001, respectively), resulting in superior CNR for evaluation of GGNs and emphysema at 100 and 80 kVp. PCD provided better HU stability for lung, ground-glass, and emphysema-equivalent foams at lower radiation dose settings with better reproducibility than EID. Additionally, PCD showed up to 10% less noise, and 11% higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.

Uptake of all-trans retinoic acid–containing aerosol by inhalation to lungs in a guinea pig model system—A pilot study

PubMed Central

Schäffer, Michael W.; Roy, Somdutta Sinha; Mukherjee, Shyamali; Ong, David E.; Das, Salil K.

2010-01-01

Systemic therapies with retinoic acid (RA) can result in toxic side effects without yielding biologically effective levels in target tissues such as lung. The authors adapted a PARI LC Star nebulizer to create a tubular system for short-term inhalation treatment of guinea pigs using a water-miscible formulation of all-trans RA (ATRA) or vehicle. Based on the initial average weight, animals received an estimated average ATRA doses of either 0.32 mg·kg−1 (low dose, 1.4 mM), or 0.62 mg·kg−1 (medium dose, 2.8 mM), or 1.26 mg·kg−1 (high dose, 5.6 mM) 20 minutes per day for 6 consecutive days. This system led to a rise of ATRA levels in lung, but not liver or plasma. Cellular lung levels of retinol, retinyl palmitate, and retinyl stearate also appeared to be unaffected (245.6 ± 10.7, 47.4 ± 3.4, and 132.8 ± 7.7 ng·g−1 wet weight, respectively). The application of this aerosolized ATRA also induced a dose-dependent protein expression of the cellular retinol-binding protein 1 (CRBP-1) in lung, without apparent harmful side effects. PMID:21043991

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

PubMed

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

1983-07-01

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

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

Clinical Application of a Hybrid RapidArc Radiotherapy Technique for Locally Advanced Lung Cancer.

PubMed

Silva, Scott R; Surucu, Murat; Steber, Jennifer; Harkenrider, Matthew M; Choi, Mehee

2017-04-01

Radiation treatment planning for locally advanced lung cancer can be technically challenging, as delivery of ≥60 Gy to large volumes with concurrent chemotherapy is often associated with significant risk of normal tissue toxicity. We clinically implemented a novel hybrid RapidArc technique in patients with lung cancer and compared these plans with 3-dimensional conformal radiotherapy and RapidArc-only plans. Hybrid RapidArc was used to treat 11 patients with locally advanced lung cancer having bulky mediastinal adenopathy. All 11 patients received concurrent chemotherapy. All underwent a 4-dimensional computed tomography planning scan. Hybrid RapidArc plans concurrently combined static (60%) and RapidArc (40%) beams. All cases were replanned using 3- to 5-field 3-dimensional conformal radiotherapy and RapidArc technique as controls. Significant reductions in dose were observed in hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans for total lung V20 and mean (-2% and -0.6 Gy); contralateral lung mean (-2.92 Gy); and esophagus V60 and mean (-16.0% and -2.2 Gy; all P < .05). Contralateral lung doses were significantly lower for hybrid RapidArc plans compared to RapidArc-only plans (all P < .05). Compared to 3-dimensional conformal radiotherapy, heart V60 and mean dose were significantly improved with hybrid RapidArc (3% vs 5%, P = .04 and 16.32 Gy vs 16.65 Gy, P = .03). However, heart V40 and V45 and maximum spinal cord dose were significantly lower with RapidArc plans compared to hybrid RapidArc plans. Conformity and homogeneity were significantly better with hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans ( P < .05). Treatment was well tolerated, with no grade 3+ toxicities. To our knowledge, this is the first report on the clinical application of hybrid RapidArc in patients with locally advanced lung cancer. Hybrid RapidArc permitted safe delivery of 60 to 66 Gy to large lung tumors with concurrent chemotherapy and demonstrated advantages for reduction in low-dose lung volumes, esophageal dose, and mean heart dose.

Pulmonary Nodule Management in Lung Cancer Screening: A Pictorial Review of Lung-RADS Version 1.0.

PubMed

Godoy, Myrna C B; Odisio, Erika G L C; Truong, Mylene T; de Groot, Patricia M; Shroff, Girish S; Erasmus, Jeremy J

2018-05-01

The number of screening-detected lung nodules is expected to increase as low-dose computed tomography screening is implemented nationally. Standardized guidelines for image acquisition, interpretation, and screen-detected nodule workup are essential to ensure a high standard of medical care and that lung cancer screening is implemented safely and cost effectively. In this article, we review the current guidelines for pulmonary nodule management in the lung cancer screening setting. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Haseeb, Syed Abdul; Ahmad, Syed Bilal; Mirza, Sika

Purpose: To assess the impact of radiation treatment delivery through patient inhomogeneities on the secondary barrier shielding requirements in IMRT treatments using Monte Carlo Simulations. Materials and Methods: Scatter factors were calculated at a distance of 1m from the center of a virtual phantom in Geant4.10.01. Phantom (30×30×30 cm{sup 3}) was inserted with lung (30×30×8 cm{sup 3}), stainless steel (5×5×5 cm{sup 3}) and aluminum (5×5×5 cm{sup 3}) to represent the inhomogeneities. Scatter factor was defined according to the NCRP-151 recommendations and was calculated for angles of 3° to 120° with respect to the beam’s central axis. A virtual radiation source,more » with energy sampled from a histogram representing 6 MV FFF beam, was used for irradiation with a field size of 15×15 cm{sup 2} and SSD of 100 cm. Results: Irradiation through the inhomogeneity affects the patient scattered dose. For high Z material inhomogeneities the scattered dose is reduced due to significant attenuation of the primary radiation. On the other hand if the inhomogeneity is a low Z material such as lung the scattered dose is higher by a maximum of 26%. The average increase in scatter factors for the lung phantom was 17% for angles between 3° and 63° compared to the homogeneous water phantom. Conclusions: In IMRT type treatments delivered through low density patient inhomogeneities (lung) the scattered dose increases significantly. Considering a large proportion of patients receiving radiation therapy for lung cancers the increase in the scattered dose should be incorporated in the shielding calculations for the secondary barriers.« less

SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

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

Best, R; Harrell, A; Geesey, C

2014-06-15

Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parametersmore » of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.« less

SU-E-T-370: Evaluating Plan Quality and Dose Delivery Accuracy of Tomotherapy SBRT Treatments for Lung Cancer

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

Blake, S; Thwaites, D; Hansen, C

2015-06-15

Purpose: This study evaluated the plan quality and dose delivery accuracy of stereotactic body radiotherapy (SBRT) helical Tomotherapy (HT) treatments for lung cancer. Results were compared with those previously reported by our group for flattening filter (FF) and flattening filter free (FFF) VMAT treatments. This work forms part of an ongoing multicentre and multisystem planning and dosimetry audit on FFF beams for lung SBRT. Methods: CT datasets and DICOM RT structures delineating the target volume and organs at risk for 6 lung cancer patients were selected. Treatment plans were generated using the HT treatment planning system. Tumour locations were classifiedmore » as near rib, near bronchial tree or in free lung with prescribed doses of 48Gy/4fr, 50Gy/5fr and 54Gy/3fr respectively. Dose constraints were specified by a modified RTOG0915 protocol used for an Australian SBRT phase II trial. Plan quality was evaluated using mean PTV dose, PTV volume receiving 100% of the prescribed dose (V100%), target conformity (CI=VD100%/VPTV) and low dose spillage (LDS=VD50%/VPTV). Planned dose distributions were compared to those measured using an ArcCheck phantom. Delivery accuracy was evaluated using a gamma-index pass rate of 95% with 3% (of max dose) and 3mm criteria. Results: Treatment plans for all patients were clinically acceptable in terms of quality and accuracy of dose delivery. The following DVH metrics are reported as averages (SD) of all plans investigated: mean PTV dose was 115.3(2.4)% of prescription, V100% was 98.8(0.9)%, CI was 1.14(0.03) and LDS was 5.02(0.37). The plans had an average gamma-index passing rate of 99.3(1.3)%. Conclusion: The results reported in this study for HT agree within 1 SD to those previously published by our group for VMAT FF and FFF lung SBRT treatments. This suggests that HT delivers lung SBRT treatments of comparable quality and delivery accuracy as VMAT using both FF and FFF beams.« less

Lung Cancer Screening With Low-Dose CT: Implementation Amid Changing Public Policy at One Health Care System.

PubMed

Begnaud, Abbie; Hall, Thomas; Allen, Tadashi

2016-01-01

Screening for lung cancer with low-dose CT has evolved rapidly in recent years since the National Lung Screening Trial (NLST) results. Subsequent professional and governmental organization guidelines have shaped policy and reimbursement for the service. Increasingly available guidance describes eligible patients and components necessary for a high-quality lung cancer screening program; however, practical instruction and implementation experience is not widely reported. We launched a lung cancer screening program in the face of reimbursement and guideline uncertainties at a large academic health center. We report our experience with implementation, including challenges and proposed solutions. Initially, we saw less referrals than expected for screening, and many patients referred for screening did not clearly meet eligibility guidelines. We educated primary care providers and implemented system tools to encourage referral of eligible patients. Moreover, in response to the Centers for Medicare & Medicaid Services (CMS) final coverage determination, we report our programmatic adaptation to meet these requirements. In addition to the components common to all quality programs, individual health delivery systems will face unique barriers related to patient population, available resources, and referral patterns.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988-1993: II. In vivo planning and dosimetry.

PubMed

Planskoy, B; Tapper, P D; Bedford, A M; Davis, F M

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were with in +/- 5% of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of 19 +/- 6.0% (1 s.d.) and in the lungs (40 patients, five slices) of 9.2 +/- 2.85% (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior-posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150 μg/L) well water arsenic levels--an exploration of the dose-response Poisson analysis.

PubMed

Lamm, Steven H; Robbins, Shayhan A; Zhou, Chao; Lu, Jun; Chen, Rusan; Feinleib, Manning

2013-02-01

To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Dosimetric comparison between 10MV-FFF and 6MV-FFF for lung SBRT

NASA Astrophysics Data System (ADS)

Durmus, I. F.; Atalay, E. D.

2017-02-01

Plans were prepared by using same non-coplanar fields and physical parameters in 6MV-FFF and 10MV-FFF energies for fourteen lung Stereotactic Body Radio Therapy (SBRT) patients. In two plans which have different energies, critic organ doses, PTV doses, quality of plans (Gradient Index (GI), Homogeneity Index (HI), Conformity Index (CI)) and Monitor Unit (MU) values were compared. Quality controls were performed with 2D-Array Iba MatriXX Evolution® dosimetry system for each plans. As a results, plan with 6MV-FFF energy give better results in terms of CI and GI values. In this way, when more conformal dose distributions were provided, there was a rapid dose decrease at out of target volume. Lower MU values were obtained in plans which was prepared with 10MV-FFF energy. In plan with 10MV-FFF energy lower MU values are obtained. Lower values in heart and spinal cord doses are founded and better results are obtained in Body and Ipsa-Lung V5, V10, V20 values with 6MV-FFF energies. When differences were very small in volume which were taken low dose (V5), these differences increased in volume which were taken high dose (V20). High dose rates can be reached by both two unfiltered energies and can be used in lung SBRT.

Submillisievert standard-pitch CT pulmonary angiography with ultra-low dose contrast media administration: A comparison to standard CT imaging

PubMed Central

Mikat, Christian; Stenzel, Elena; Erfanian, Youssef; Wetter, Axel; Schlosser, Thomas; Forsting, Michael

2017-01-01

Objectives To evaluate the image quality and radiation dose of submillisievert standard-pitch CT pulmonary angiography (CTPA) with ultra-low dose contrast media administration in comparison to standard CTPA. Materials and methods Hundred patients (56 females, 44 males, mean age 69.6±15.4 years; median BMI: 26.6, IQR: 5.9) with suspected pulmonary embolism were examined with two different protocols (n = 50 each, group A: 80 kVp, ref. mAs 115, 25 ml of contrast medium; group B: 100 kVp, ref. mAs 150, 60 ml of contrast medium) using a dual-source CT equipped with automated exposure control. Objective and subjective image qualities, radiation exposure as well as the frequency of pulmonary embolism were evaluated. Results There was no significant difference in subjective image quality scores between two groups regarding pulmonary arteries (p = 0.776), whereby the interobserver agreement was excellent (group A: k = 0.9; group B k = 1.0). Objective image analysis revealed that signal intensities (SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the pulmonary arteries were equal or significantly higher in group B. There was no significant difference in the frequency of pulmonary embolism (p = 0.65). Using the low dose and low contrast media protocol resulted in a radiation dose reduction by 71.8% (2.4 vs. 0.7 mSv; p<0.001). Conclusions This 80 kVp standard pitch CTPA protocol with 25 ml contrast agent volume can obtain sufficient image quality to exclude or diagnose pulmonary emboli while reducing radiation dose by approximately 71%. PMID:29045463

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

NASA Technical Reports Server (NTRS)

Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

2014-01-01

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement.

PubMed

Moyer, Virginia A

2014-03-04

Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lung cancer. The USPSTF reviewed the evidence on the efficacy of low-dose computed tomography, chest radiography, and sputum cytologic evaluation for lung cancer screening in asymptomatic persons who are at average or high risk for lung cancer (current or former smokers) and the benefits and harms of these screening tests and of surgical resection of early-stage non-small cell lung cancer. The USPSTF also commissioned modeling studies to provide information about the optimum age at which to begin and end screening, the optimum screening interval, and the relative benefits and harms of different screening strategies. This recommendation applies to asymptomatic adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation).

Long-term stable lung function and second uncomplicated pregnancy on sirolimus in lymphangioleiomyomatosis (LAM).

PubMed

Faehling, Martin; Wienhausen-Wilke, Vera; Fallscheer, Sabine; Trinajstic-Schulz, B; Weber, J; Leschke, Matthias

2015-09-14

We present a patient with lymphangioleiomyomatosis (LAM) on long-term sirolimus (now 79 months) who has had a second successful pregnancy. The second pregnancy on uninterrupted low-dose sirolimus (plasma levels 3-5 mg/L) was uncomplicated both with respect to mother and child suggesting that low-dose sirolimus might be safe in selected pregnant patients with stable LAM. The long-term time course in this patient is in agreement with recent reports of a long-term beneficial effect of sirolimus in LAM. In this patient, the pregnancies did not seem to impair the long-term improvement of lung-function on sirolimus.

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

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

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 placedmore » 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.« less

A computer simulated phantom study of tomotherapy dose optimization based on probability density functions (PDF) and potential errors caused by low reproducibility of PDF.

PubMed

Sheng, Ke; Cai, Jing; Brookeman, James; Molloy, Janelle; Christopher, John; Read, Paul

2006-09-01

Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can be converted to a probability density function (PDF), which describes the probability of the tumor at a certain position, for PDF based treatment planning. Using this method in simulated sequential tomotherapy, we study the dose reduction of normal tissues and more important, the effect of PDF reproducibility on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The first PDF was accumulated from a 300 s scan and the second PDF was calculated from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam fluences based on the second PDF were delivered to the hypothetical gross target volume (GTV) of a lung phantom that moved following the first PDF The reproducibility between two PDFs varied from low (78%) to high (94.8%) when the second scan time increased from 5 s to 300 s. When a highly reproducible PDF was used in optimization, the dose coverage of GTV was maintained; phantom lung receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom lung dose was reduced by 9.6%. However, optimization based on PDF with low reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased nearly exponentially as the PDF error increased. Therefore, although the dose of the tumor surrounding tissue can be theoretically reduced by PDF based treatment planning, the reliability and applicability of this method highly depend on if a reproducible PDF exists and is measurable. By correlating the dosimetric error and PDF error together, a useful guideline for PDF data acquisition and patient qualification for PDF based planning can be derived.

A computer simulated phantom study of tomotherapy dose optimization based on probability density functions (PDF) and potential errors caused by low reproducibility of PDF

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

Sheng, Ke; Cai Jing; Brookeman, James

2006-09-15

Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can be converted to a probability density function (PDF), which describes the probability of the tumor at a certain position, for PDF based treatment planning. Using this method in simulated sequential tomotherapy, we study the dose reduction of normal tissues and more important, the effect of PDF reproducibility on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The first PDF was accumulated from a 300 s scan and the second PDF wasmore » calculated from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam fluences based on the second PDF were delivered to the hypothetical gross target volume (GTV) of a lung phantom that moved following the first PDF. The reproducibility between two PDFs varied from low (78%) to high (94.8%) when the second scan time increased from 5 s to 300 s. When a highly reproducible PDF was used in optimization, the dose coverage of GTV was maintained; phantom lung receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom lung dose was reduced by 9.6%. However, optimization based on PDF with low reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased nearly exponentially as the PDF error increased. Therefore, although the dose of the tumor surrounding tissue can be theoretically reduced by PDF based treatment planning, the reliability and applicability of this method highly depend on if a reproducible PDF exists and is measurable. By correlating the dosimetric error and PDF error together, a useful guideline for PDF data acquisition and patient qualification for PDF based planning can be derived.« less

Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

PubMed Central

Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Results Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Conclusion Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung. PMID:21228937

Collateral ventilation to congenital hyperlucent lung lesions assessed on xenon-enhanced dynamic dual-energy CT: an initial experience.

PubMed

Goo, Hyun Woo; Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung.

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

PubMed

Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Poster - 36: Effect of Planning Target Volume Coverage on the Dose Delivered in Lung Radiotherapy

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

Dekker, Chris; Wierzbicki, Marcin

2016-08-15

Purpose: In lung radiotherapy, breathing motion may be encompassed by contouring the internal target volume (ITV). Remaining uncertainties are included in a geometrical expansion to the planning target volume (PTV). In IMRT, the treatment is then optimized until a desired PTV fraction is covered by the appropriate dose. The resulting beams often carry high fluence in the PTV margin to overcome low lung density and to generate steep dose gradients. During treatment, the high density tumour can enter the PTV margin, potentially increasing target dose. Thus, planning lung IMRT with a reduced PTV dose may still achieve the desired ITVmore » dose during treatment. Methods: A retrospective analysis was carried out with 25 IMRT plans prescribed to 63 Gy in 30 fractions. The plans were re-normalized to cover various fractions of the PTV by different isodose lines. For each case, the isocentre was moved using 125 shifts derived from all 3D combinations of 0 mm, (PTV margin - 1 mm), and PTV margin. After each shift, the dose was recomputed to approximate the delivered dose. Results and Conclusion: Our plans typically cover 95% of the PTV by 95% of the dose. Reducing the PTV covered to 94% did not significantly reduce the delivered ITV doses for (PTV margin - 1 mm) shifts. Target doses were reduced significantly for all other shifts and planning goals studied. Thus, a reduced planning goal will likely deliver the desired target dose as long as the ITV rarely enters the last mm of the PTV margin.« less

Western Australian cigarette smokers have fewer small lung nodules than North Americans on CT screening for lung cancer.

PubMed

Murray, C P; Wong, P M; Louw, J; Waterer, G W

2009-08-01

To determine the prevalence of small lung nodules on low-dose helical computed tomography (CT) in a Western Australian cohort of asymptomatic long-term cigarette smokers and to compare this with a large, similarly derived cohort of North Americans from the Mayo Clinic Lung Cancer Screening Trial. Forty-nine asymptomatic long-term cigarette smokers of minimum age 50 years underwent a low-dose 64-slice helical CT of the lungs. Images were viewed on a soft copy reporting station with thin section axial and coronal images, maximum intensity projection images, and advanced image manipulation tools. The prevalence of all nodules was 39%, significantly lower than the Mayo Clinic cohort prevalence of 51% (P < 0.01, Fisher's exact test), despite the use of more advanced imaging technology and image manipulation designed to increase the sensitivity for nodules. The prevalence of small nodules in asymptomatic long-term cigarette smokers in Western Australia is high, though significantly less than that found in a large study in North America. The authors postulate this is due to the relatively low rates of mycobacterium tuberculosis and soil-derived fungal pulmonary infections in Western Australia, as well as a lower degree of urban air pollution.

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.

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.

CT acquisition technique and quantitative analysis of the lung parenchyma: variability and corrections

NASA Astrophysics Data System (ADS)

Zheng, Bin; Leader, J. K.; Coxson, Harvey O.; Scuirba, Frank C.; Fuhrman, Carl R.; Balkan, Arzu; Weissfeld, Joel L.; Maitz, Glenn S.; Gur, David

2006-03-01

The fraction of lung voxels below a pixel value "cut-off" has been correlated with pathologic estimates of emphysema. We performed a "standard" quantitative CT (QCT) lung analysis using a -950 HU cut-off to determine the volume fraction of emphysema (below the cut-off) and a "corrected" QCT analysis after removing small group (5 and 10 pixels) of connected pixels ("blobs") below the cut-off. CT examinations two dataset of 15 subjects each with a range of visible emphysema and pulmonary obstruction were acquired at "low-dose and conventional dose reconstructed using a high-spatial frequency kernel at 2.5 mm section thickness for the same subject. The "blob" size (i.e., connected-pixels) removed was inversely related to the computed fraction of emphysema. The slopes of emphysema fraction versus blob size were 0.013, 0.009, and 0.005 for subjects with both no emphysema and no pulmonary obstruction, moderate emphysema and pulmonary obstruction, and severe emphysema and severe pulmonary obstruction, respectively. The slopes of emphysema fraction versus blob size were 0.008 and 0.006 for low-dose and conventional CT examinations, respectively. The small blobs of pixels removed are most likely CT image artifacts and do not represent actual emphysema. The magnitude of the blob correction was appropriately associated with COPD severity. The blob correction appears to be applicable to QCT analysis in low-dose and conventional CT exams.

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;

Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein.

PubMed

Atefeh, Zamanian; Vahid, Changizi; Hasan, Nedaie; Saeed, Amanpour; Mahnaz, Haddadi

2016-01-01

Gioblastoma multiforme as a chemoresistant and radioresistant malignant cell line needs to novel strategies to treatment. Low-dose hyper-radiosensitivity (LDHRS) seems to be an effective phenomenon to irradiation that can save normal brain fibroblasts. Genistein which is a soy isoflavone can be cytotoxic in some tumor cell lines. So we determined to study the effect of combining these two treatment modalities. After 30 hours incubation with Genistein in different concentrations on U87MG cell line, proliferation and clonogenicity were conducted by both clonogenic and MTT assays. A conventional 2Gy radiation dose was compared with 10 doses of 0.2Gy gamma irradiation with 3 minutes and 1 hour intervals. Finally, concurrent effect of these modalities was assessed. Based on acquired cell doubling time (30 hours), one doubling time treatment by Genistein could decrease clonogenicity. U87MG cell line exhibited HRS at low dose irradiations. 2Gy irradiation was more effective than ultra-fractionation methods in comparison with control group. All groups with 50uM concentration of Genistein showed decrease in the survival. This decrease compared with control group, in 10x0.2Gy with 3 minutes intervals plus 50uM Genistein was significant and for groups with the same dose of Genistein but along with continuous 2Gy was more significant. In one day treatment regimen, 10x0.2Gy ultra-fractionation with 3 minutes and 1 hour intervals seems to be less effective than conventional 2Gy irradiation, however adding 50uM Genistein can decrease survival more. Although 2Gy conventional dose plus 50uM Genistein was the most effective regimen. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of an Ultra-Low Power Reed Solomon Encoder for NASA's Space Technology 5 Mission

NASA Technical Reports Server (NTRS)

Lei, K. E.; Xapsos, M. A.; Poivey, C.; LaBel, K. A.; Stone, R. F.; Yeh, P-S.; Gambles, J.; Hass, J.; Maki, G.; Murguia, J.

2003-01-01

Radiation test results and analyses are presented for ultra-low power Reed Solomon encoder circuits that are being considered for use on the Space Technology 5 (ST5) mission. The total ionizing dose tolerance is in excess of 100 krad(Si) and is due to the low supply voltage and the use of back-bias, which suppresses radiation-induced leakage currents in the n-channel devices. The circuits do not latch-up for ion LET values of at least 90 MeV-sq cm/mg. A hardened-by-design approach to SEU has achieved an upset threshold of about 20 MeV-sq cm/mg. The SEU rate expected for these circuits in the geosynchronous transfer orbit of ST5 is low.

SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

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

Qu, H; Xia, P; Yu, N

Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

Initial clinical evaluation of stationary digital chest tomosynthesis

NASA Astrophysics Data System (ADS)

Hartman, Allison E.; Shan, Jing; Wu, Gongting; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping; Heath, Michael; Wang, Xiaohui; Foos, David

2016-03-01

Computed Tomography (CT) is the gold standard for image evaluation of lung disease, including lung cancer and cystic fibrosis. It provides detailed information of the lung anatomy and lesions, but at a relatively high cost and high dose of radiation. Chest radiography is a low dose imaging modality but it has low sensitivity. Digital chest tomosynthesis (DCT) is an imaging modality that produces 3D images by collecting x-ray projection images over a limited angle. DCT is less expensive than CT and requires about 1/10th the dose of radiation. Commercial DCT systems acquire the projection images by mechanically scanning an x-ray tube. The movement of the tube head limits acquisition speed. We recently demonstrated the feasibility of stationary digital chest tomosynthesis (s-DCT) using a carbon nanotube (CNT) x-ray source array in benchtop phantom studies. The stationary x-ray source allows for fast image acquisition. The objective of this study is to demonstrate the feasibility of s-DCT for patient imaging. We have successfully imaged 31 patients. Preliminary evaluation by board certified radiologists suggests good depiction of thoracic anatomy and pathology.

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.

Reflections on the Implementation of Low-Dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain.

PubMed

Garrido, Pilar; Sánchez, Marcelo; Belda Sanchis, José; Moreno Mata, Nicolás; Artal, Ángel; Gayete, Ángel; Matilla González, José María; Galbis Caravajal, José Marcelo; Isla, Dolores; Paz-Ares, Luis; Seijo, Luis M

2017-10-01

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM). Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Radiation risks in lung cancer screening programs: a comparison with nuclear industry workers and atomic bomb survivors.

PubMed

McCunney, Robert J; Li, Jessica

2014-03-01

The National Lung Cancer Screening Trial (NLST) demonstrated that screening with low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%, respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full-chest CT scanning, the major diagnostic study used to follow up nodules, may involve a dose of 8 mSv. Radiation associated with CT scanning and other diagnostic studies to follow up nodules may present an independent risk of lung cancer. On the basis of the NLST, we estimated the incidence and prevalence of nodules detected in screening programs. We followed the Fleischner guidelines for follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor studies to assess the risk of lung cancer from radiation associated with long-term lung cancer screening programs. The findings indicate that a 55-year-old lung screening participant may experience a cumulative radiation exposure of up to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures exceed those of nuclear workers and atomic bomb survivors. This assessment suggests that long-term (20-30 years) LDCT screening programs are associated with nontrivial cumulative radiation doses. Current lung cancer screening protocols, if conducted over 20- to 30-year periods, can independently increase the risk of lung cancer beyond cigarette smoking as a result of cumulative radiation exposure. Radiation exposures from LDCT screening and follow-up diagnostic procedures exceed lifetime radiation exposures among nuclear power workers and atomic bomb survivors.

[Effect of Buzhong Yiqi decoction on PI3K and AKT in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor].

PubMed

Liu, Ya-Li; Wang, Ying; Yi, Jia-Li; Jing, Huan; Liu, Chun-Ying

2014-05-01

To explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor. Totally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung. Buzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P < 0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P < 0.05), but without statistical difference compared with the blank control group. Among nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

TH-AB-207A-12: CT Lung Cancer Screening and the Effects of Further Dose Reduction On CAD Performance

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

Young, S; Lo, P; Hoffman, J

Purpose: CT lung screening is already performed at low doses. In this study, we investigated the effects of further dose reduction on a lung-nodule CAD detection algorithm. Methods: The original raw CT data and images from 348 patients were obtained from our local database of National Lung Screening Trial (NLST) cases. 61 patients (17.5%) had at least one nodule reported on the NLST reader forms. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel. Based onmore » a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, a CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST forms. Sensitivities and false-positive rates (FPR) were calculated for each dose level, with a sub-analysis by nodule LungRADS category. Results: For larger category 4 nodules, median sensitivities were 100% at all three dose levels, and mean sensitivity decreased with dose. For the more challenging category 2 and 3 nodules, the dose dependence was less obvious. Overall, mean subject-level sensitivity varied from 38.5% at 100% dose to 40.4% at 50% dose, a difference of only 1.9%. However, median FPR quadrupled from 1 per case at 100% dose to 4 per case at 25% dose. Conclusions: Dose reduction affected nodule detectability differently depending on the LungRADS category, and FPR was very sensitive at sub-screening levels. Care should be taken to adapt CAD for the very challenging noise characteristics of screening. Funding support: NIH U01 CA181156; Disclosures (McNitt-Gray): Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

[Effect of substance P on cardiac autonomic nervous function in rats].

PubMed

Deng, Lijun; Li, Jing; Yan, Fuping; Lu, Jie

2009-12-01

Forty SD rats were divided into 5 groups: control group, SP groups (5 microg/kg,10 microg/kg, 20 microg/kg) and spantide II plus SP group. An analysis of heart rate variability (HRV) was used to detect the changes of HRV parameters before and after intravenous injection of SP in order to investigate the effect of substance P on cardiac autonomic nervous function and the corresponding mechanism. (1) There were significant differences in most HRV parameters for the three different doses of SP. Mean heart period (MHP), absolute power of ultra-low frequency and high frequency band (APU, APH), total power (TPV) and ratio of power in ultra-low to high frequency band (RUH) increased, while mean heart rate (MHR) and chaos intensity (HCC) decreased during the 30 minutes. Each peak amplitude of HRV parameters went higher and showed up ahead of the upward doses of SP. (2) Significant change was seen in each of the parameters between spantide II plus SP group and high-dose SP group. These data idicate that, after intravenous injection of different doses of SP, both cardiac sympathetic nervous system activity and parasympathetic nervous system activity increase, and the function of cardiac autonomic nervous becomes instable and unbalanced. The effect of SP may be dose dependent, and it is possibly mediated by neurokinin-1(NK-1) receptor.

Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.

PubMed

Tucker, Susan L; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K; Liao, Zhongxing

2013-02-01

To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot"). Copyright © 2013 Elsevier Inc. All rights reserved.

GENE EXPRESSION CHANGES IN MOUSE BLADDER TISSUE IN RESPONSE TO INORGANIC ARSENIC

EPA Science Inventory

Chronic human exposures to high arsenic concentrations are associated with lung, skin, and bladder cancer. Considerable controversy exists concerning arsenic mode of action and low dose extrapolation. This investigation was designed to identify dose-response changes in gene expre...

CT screening for lung cancer: Importance of emphysema for never smokers and smokers.

PubMed

Henschke, Claudia I; Yip, Rowena; Boffetta, Paolo; Markowitz, Steven; Miller, Albert; Hanaoka, Takaomi; Wu, Ning; Zulueta, Javier J; Yankelevitz, David F

2015-04-01

To address the prevalence of lung cancer in high and low-risk people according to their smoking history, age, and CT findings of emphysema. We reviewed the baseline low-dose CT scans of 62,124 current, former and never smokers, aged 40-90 to determine the prevalence of lung cancer. We performed logistic regression analysis of the prevalence of lung cancer to determine the odds ratio (OR) for emphysema, conditionally on age, female gender, and ethnicity. The prevalence of lung cancer was 1.4% (95% CI: 1.3-1.6) for current smokers, 1.1% (95% CI: 1.0-1.2) for former smokers, and 0.4% (95% CI: 0.3-0.6) for never smokers. Emphysema was identified in 28.5% (6,684), 20.6% (5,422), and 1.6% (194) of current, former, and never smokers, respectively. The prevalence of lung cancer among current smokers was 1.1% for those without emphysema vs. 2.3% for those with emphysema (odds ratio [OR] 1.8; 95% confidence interval [CI]: 1.4-2.2) and the corresponding difference for former smokers was 0.9% vs. 1.8% (OR: 1.7; 95% CI: 1.3-2.2), and for never smokers, it was 0.4% vs. 2.6% (OR: 6.3; 95% CI: 2.4-16.9). Identification of emphysema in low-dose CT scans increases the risk of lung cancer and is important in determining follow-up of current, former, and never smokers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening

PubMed Central

Walter, Joan E.; Oudkerk, Matthijs

2017-01-01

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines. PMID:28331823

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988 - 1993: II. In vivo planning and dosimetry

NASA Astrophysics Data System (ADS)

Planskoy, B.; Tapper, P. D.; Bedford, A. M.; Davis, F. M.

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were within of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of (1 s.d.) and in the lungs (40 patients, five slices) of (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior - posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

N-acetyl cysteine improves the effects of corticosteroids in a mouse model of chlorine-induced acute lung injury.

PubMed

Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders; Jonasson, Sofia

2015-02-03

Chlorine (Cl2) causes tissue damage and a neutrophilic inflammatory response in the airways manifested by pronounced airway hyperreactivity (AHR). The importance of early anti-inflammatory treatment has previously been addressed. In the previous study, both high-dose and low-dose of dexamethasone (DEX) decreased the risk of developing delayed effects, such as persistent lung injuries, while only high-dose treatment could significantly counteract acute-phase effects. One aim of this study was to evaluate whether a low-dose of DEX in combination with the antioxidant N-acetyl cysteine (NAC) and if different treatments (Triptolide, Reparixin and Rolipram) administered 1h after Cl2-exposure could improve protection against acute lung injury in Cl2-exposed mice. BALB/c mice were exposed to 300 ppm Cl2 during 15 min. Assessment of AHR and inflammatory cells in bronchoalveolar lavage was analyzed 24h post exposure. Neither of DEX nor NAC reduced the AHR and displayed only minor effects on inflammatory cell influx when given as separate treatments. When given in combination, a protective effect on AHR and a significant reduction in inflammatory cells (neutrophils) was observed. Neither of triptolide, Reparixin nor Rolipram had an effect on AHR but Triptolide had major effect on the inflammatory cell influx. Treatments did not reduce the concentration of either fibrinogen or plasminogen activator inhibitor-1 in serum, thereby supporting the theory that the inflammatory response is not solely limited to the lung. These results provide a foundation for future studies aimed at identifying new concepts for treatment of chemical-induced lung injury. Studies addressing combination of anti-inflammatory and antioxidant treatment are highly motivated. Copyright © 2014. Published by Elsevier Ireland Ltd.

Traffic aerosol lobar doses deposited in the human respiratory system.

PubMed

Manigrasso, Maurizio; Vernale, Claudio; Avino, Pasquale

2017-06-01

Aerosol pollution in urban environments has been recognized to be responsible for important pathologies of the cardiovascular and respiratory systems. In this perspective, great attention has been addressed to Ultra Fine Particles (UFPs < 100 nm), because they efficiently penetrate into the respiratory system and are capable of translocating from the airways into the blood circulation. This paper describes the aerosol regional doses deposited in the human respiratory system in a high-traffic urban area. The aerosol measurements were carried out on a curbside in downtown Rome, on a street characterized by a high density of autovehicular traffic. Aerosol number-size distributions were measured by means of a Fast Mobility Particle Sizer in the range from 5.6 to 560 nm with a 1 s time resolution. Dosimetry estimates were performed with the Multiple-Path Particle Dosimetry model by means of the stochastic lung model. The exposure scenario close to traffic is represented by a sequence of short-term peak exposures: about 6.6 × 10 10 particles are deposited hourly into the respiratory system. After 1 h of exposure in proximity of traffic, 1.29 × 10 10 , 1.88 × 10 10 , and 3.45 × 10 10 particles are deposited in the head, tracheobronchial, and alveolar regions. More than 95 % of such doses are represented by UFPs. Finally, according to the greater dose estimated, the right lung lobes are expected to be more susceptible to respiratory pathologies than the left lobes.

Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

PubMed

Shi, Shiming; Zeng, Zhaochong; Ye, Luxi; Huang, Yan; He, Jian

2017-06-01

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Algorithm of pulmonary emphysema extraction using thoracic 3-D CT images

NASA Astrophysics Data System (ADS)

Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Ohmatsu, Hironobu; Tominaga, Keigo; Eguchi, Kenji; Moriyama, Noriyuki

2008-03-01

Emphysema patients have the tendency to increase due to aging and smoking. Emphysematous disease destroys alveolus and to repair is impossible, thus early detection is essential. CT value of lung tissue decreases due to the destruction of lung structure. This CT value becomes lower than the normal lung- low density absorption region or referred to as Low Attenuation Area (LAA). So far, the conventional way of extracting LAA by simple thresholding has been proposed. However, the CT value of CT image fluctuates due to the measurement conditions, with various bias components such as inspiration, expiration and congestion. It is therefore necessary to consider these bias components in the extraction of LAA. We removed these bias components and we proposed LAA extraction algorithm. This algorithm has been applied to the phantom image. Then, by using the low dose CT(normal: 30 cases, obstructive lung disease: 26 cases), we extracted early stage LAA and quantitatively analyzed lung lobes using lung structure.

Comparison of image quality, myocardial perfusion, and LV function between standard imaging and single-injection ultra-low-dose imaging using a high-efficiency SPECT camera: the MILLISIEVERT study

PubMed Central

Einstein, Andrew J.; Blankstein, Ron; Andrews, Howard; Fish, Mathews; Padgett, Richard; Hayes, Sean W.; Friedman, John D.; Qureshi, Mehreen; Rakotoarivelo, Harivony; Slomka, Piotr; Nakazato, Ryo; Bokhari, Sabahat; Di Carli, Marcello; Berman, Daniel S.

2015-01-01

SPECT myocardial perfusion imaging (MPI) plays a central role in coronary artery disease diagnosis; but concerns exist regarding its radiation burden. Compared to standard Anger-SPECT (A-SPECT) cameras, new high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer potential to maintain image quality (IQ), while reducing administered activity and thus radiation dose to patients. No previous study has compared IQ, interpretation, total perfusion deficit (TPD), or ejection fraction (EF) in patients receiving both ultra-low-dose (ULD) imaging on a HE-SPECT camera and standard low-dose (SLD) A-SPECT imaging. Methods We compared ULD-HE-SPECT to SLD-A-SPECT imaging by dividing the rest dose in 101 patients at 3 sites scheduled to undergo clinical A-SPECT MPI using a same day rest/stress Tc-99m protocol. Patients received HE-SPECT imaging following an initial ~130 MBq (3.5mCi) dose, and SLD-A-SPECT imaging following the remainder of the planned dose. Images were scored visually by 2 blinded readers for IQ and summed rest score (SRS). TPD and EF were assessed quantitatively. Results Mean activity was 134 MBq (3.62 mCi) for ULD-HE-SPECT (effective dose 1.15 mSv) and 278 MBq (7.50 mCi, 2.39 mSv) for SLD-A-SPECT. Overall IQ was superior for ULD-HE-SPECT (p<0.0001), with twice as many studies graded excellent quality. Extracardiac activity and overall perfusion assessment were similar. Between-method correlations were high for SRS (r=0.87), TPD (r=0.91), and EF (r=0.88). Conclusion ULD-HE-SPECT rest imaging correlates highly with SLD-A-SPECT. It has improved image quality, comparable extracardiac activity, and achieves radiation dose reduction to 1 mSv for a single injection. PMID:24982439

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

NASA Astrophysics Data System (ADS)

Cadena, M. S. Reyes; Chapul, L. Sánchez; Pérez, Javiér; García, M. N. Jiménez; López, M. A. Jiménez; Espíndola, M. E. Sánchez; Perez, R. Paniagua; Hernández, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodríguez

2008-08-01

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-β) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

Quantitative assessment of emphysema from whole lung CT scans: comparison with visual grading

NASA Astrophysics Data System (ADS)

Keller, Brad M.; Reeves, Anthony P.; Apanosovich, Tatiyana V.; Wang, Jianwei; Yankelevitz, David F.; Henschke, Claudia I.

2009-02-01

Emphysema is a disease of the lungs that destroys the alveolar air sacs and induces long-term respiratory dysfunction. CT scans allow for imaging of the anatomical basis of emphysema and for visual assessment by radiologists of the extent present in the lungs. Several measures have been introduced for the quantification of the extent of disease directly from CT data in order to add to the qualitative assessments made by radiologists. In this paper we compare emphysema index, mean lung density, histogram percentiles, and the fractal dimension to visual grade in order to evaluate the predictability of radiologist visual scoring of emphysema from low-dose CT scans through quantitative scores, in order to determine which measures can be useful as surrogates for visual assessment. All measures were computed over nine divisions of the lung field (whole lung, individual lungs, and upper/middle/lower thirds of each lung) for each of 148 low-dose, whole lung scans. In addition, a visual grade of each section was also given by an expert radiologist. One-way ANOVA and multinomial logistic regression were used to determine the ability of the measures to predict visual grade from quantitative score. We found that all measures were able to distinguish between normal and severe grades (p<0.01), and between mild/moderate and all other grades (p<0.05). However, no measure was able to distinguish between mild and moderate cases. Approximately 65% prediction accuracy was achieved from using quantitative score to predict visual grade, with 73% if mild and moderate cases are considered as a single class.

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

PubMed

Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

2013-12-01

Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

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

Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz

Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillatedmore » water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.« less

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model.

PubMed

Salama, Abeer; Hegazy, Rehab; Hassan, Azza

2016-01-01

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

PubMed Central

Salama, Abeer; Hassan, Azza

2016-01-01

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds. PMID:27997619

Reliability testing of ultra-low noise InGaAs quad photoreceivers

NASA Astrophysics Data System (ADS)

Joshi, Abhay M.; Datta, Shubhashish; Prasad, Narasimha; Sivertz, Michael

2018-02-01

We have developed ultra-low noise quadrant InGaAs photoreceivers for multiple applications ranging from Laser Interferometric Gravitional Wave Detection, to 3D Wind Profiling. Devices with diameters of 0.5 mm, 1mm, and 2 mm were processed, with the nominal capacitance of a single quadrant of a 1 mm quad photodiode being 2.5 pF. The 1 mm diameter InGaAs quad photoreceivers, using a low-noise, bipolar-input OpAmp circuitry exhibit an equivalent input noise per quadrant of <1.7 pA/√Hz in 2 to 20 MHz frequency range. The InGaAs Quad Photoreceivers have undergone the following reliability tests: 30 MeV Proton Radiation up to a Total Ionizing Dose (TID) of 50 krad, Mechanical Shock, and Sinusoidal Vibration.

Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

PubMed

Sestini, Stefano; Boeri, Mattia; Marchiano, Alfonso; Pelosi, Giuseppe; Galeone, Carlotta; Verri, Carla; Suatoni, Paola; Sverzellati, Nicola; La Vecchia, Carlo; Sozzi, Gabriella; Pastorino, Ugo

2015-10-20

Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers.Between 2000 and 2010, 3411 heavy smokers enrolled in two screening programmes, underwent annual or biennial LDCT. During the first five years of screening, 84 lung cancer patients were classified according to one of the three MSC levels of risk: high, intermediate or low. Kaplan-Meier survival analysis was performed according to MSC and clinico-pathological information. Follow-up MSC analysis was performed on longitudinal plasma samples (n = 100) collected from 31 patients before and after surgical resection.Five-year survival was 88.9% for low risk, 79.5% for intermediate risk and 40.1% for high risk MSC (p = 0.001). The prognostic power of MSC persisted after adjusting for tumor stage (p = 0.02) and when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (p < 0.001). The MSC risk level decreased after surgery in 76% of the 25 high-intermediate subjects who remained disease free, whereas in relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression.These results encourage exploiting the MSC test for lung cancer monitoring in LDCT screening for lung cancer.

Acute antidepressant effects of right unilateral ultra-brief ECT: a double-blind randomised controlled trial.

PubMed

Mayur, Prashanth; Byth, Karen; Harris, Anthony

2013-07-01

Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). The small sample study in the study increases the likelihood of type 2 error. In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT. Copyright © 2012 Elsevier B.V. All rights reserved.

Lung Cancer Screening.

PubMed

Hoffman, Richard M; Sanchez, Rolando

2017-07-01

Lung cancer is the leading cause of cancer death in the United States. More than 80% of these deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden. The National Lung Screening Trial showed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography. The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years. Published by Elsevier Inc.

Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210.

PubMed

Little, J B; Kennedy, A R; McGandy, R B

1975-05-16

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.

PubMed

Wang, Yan; Feinstein, Sheldon I; Manevich, Yefim; Ho, Ye-Shih; Fisher, Aron B

2006-01-01

Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

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

Jonasson, Sofia, E-mail: sofia.jonasson@foi.se; Wigenstam, Elisabeth; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå

Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of themore » corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as AHR in Cl{sub 2}-induced lung injury. • Early medical intervention of corticosteroids is of importance. • Treatment with corticosteroids alone is insufficient to counteract acute lung injury.« less

Serum metabolic profiling study of lung cancer using ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

PubMed

Li, Yanjie; Song, Xue; Zhao, Xinjie; Zou, Lijuan; Xu, Guowang

2014-09-01

Lung cancer is currently the leading cause of cancer-related mortality worldwide. It is, therefore, important to enhance understanding and add a new auxiliary detection tool of lung cancer. In this work, serum metabolic characteristics of lung cancer were investigated with a non-targeted metabolomics method. The metabolic profiling of 23 patients with lung cancer and 23 healthy controls were analyzed using ultra high performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant analysis (PLS-DA) model of the metabolic data allowed the clear separation of the lung cancer patients from the healthy controls. In total, 27 differential metabolites were identified, which were mostly related to the perturbation of lipid metabolism, including choline, free fatty acids, lysophosphatidylcholines, etc. Choline and linoleic acid were defined as one combinational biomarker using binary logistic regression, which was supported by the validation with a smaller sample-set (9 patients and 9 healthy controls). These findings show that LC/MS-based serum metabolic profiling has potential application in complementary identification of lung cancer patients, and could be a powerful tool for cancer research. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension.

PubMed

Shaw, Duncan E; Baig, Ferheen; Bruce, Ian; Chamoin, Sylvie; Collingwood, Stephen P; Cross, Sarah; Dayal, Satish; Drückes, Peter; Furet, Pascal; Furminger, Vikki; Haggart, Deborah; Hussey, Martin; Konstantinova, Irena; Loren, Jon C; Molteni, Valentina; Roberts, Sonia; Reilly, John; Saunders, Alex M; Stringer, Rowan; Sviridenko, Lilya; Thomas, Matthew; Thomson, Christopher G; Tomlins, Christine; Wen, Ben; Yeh, Vince; Pearce, Andrew C

2016-09-08

A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro:in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

PubMed

Hesterberg, T W; Axten, C; McConnell, E E; Oberdörster, G; Everitt, J; Miiller, W C; Chevalier, J; Chase, G R; Thevenaz, P

1997-09-01

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

PubMed Central

Hesterberg, T W; Axten, C; McConnell, E E; Oberdörster, G; Everitt, J; Miiller, W C; Chevalier, J; Chase, G R; Thevenaz, P

1997-01-01

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups. PMID:9400728

Down to 2 nm Ultra Shallow Junctions : Fabrication by IBS Plasma Immersion Ion Implantation Prototype PULSION registered

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

Torregrosa, Frank; Etienne, Hasnaa; Mathieu, Gilles

Classical beam line implantation is limited in low energies and cannot achieve P+/N junctions requirements for <45nm node. Compared to conventional beam line ion implantation, limited to a minimum of about 200 eV, the efficiency of Plasma Immersion Ion Implantation (PIII) is no more to prove for the realization of Ultra Shallow Junctions (USJ) in semiconductor applications: this technique allows to get ultimate shallow profiles (as implanted) thanks to no lower limitation of energy and offers high dose rate. In the field of the European consortium NANOCMOS, Ultra Shallow Junctions implanted on a semi-industrial PIII prototype (PULSION registered ) designedmore » by the French company IBS, have been studied. Ultra shallow junctions implanted with BF3 at acceleration voltages down to 20V were realized. Contamination level, homogeneity and depth profile are studied. The SIMS profiles obtained show the capability to make ultra shallow profiles (as implanted) down to 2nm.« less

Feasibility study of the diagnosis and monitoring of cystic fibrosis in pediatric patients using stationary digital chest tomosynthesis

NASA Astrophysics Data System (ADS)

Potuzko, Marci; Shan, Jing; Pearce, Caleb; Lee, Yueh Z.; Lu, Jianping; Zhou, Otto

2015-03-01

Digital chest tomosynthesis (DCT) is a 3D imaging modality which has been shown to approach the diagnostic capability of CT, but uses only one-tenth the radiation dose of CT. One limitation of current commercial DCT is the mechanical motion of the x-ray source which prolongs image acquisition time and introduces motion blurring in images. By using a carbon nanotube (CNT) x-ray source array, we have developed a stationary digital chest tomosynthesis (s- DCT) system which can acquire tomosynthesis images without mechanical motion, thus enhancing the image quality. The low dose and high quality 3D image makes the s-DCT system a viable imaging tool for monitoring cystic fibrosis (CF) patients. The low dose is especially important in pediatric patients who are both more radiosensitive and have a longer lifespan for radiation symptoms to develop. The purpose of this research is to evaluate the feasibility of using s-DCT as a faster, lower dose means for diagnosis and monitoring of CF in pediatric patients. We have created an imaging phantom by injecting a gelatinous mucus substitute into porcine lungs and imaging the lungs from within an anthropomorphic hollow chest phantom in order to mimic the human conditions of a CF patient in the laboratory setting. We have found that our s-DCT images show evidence of mucus plugging in the lungs and provide a clear picture of the airways in the lung, allowing for the possibility of using s- DCT to supplement or replace CT as the imaging modality for CF patients.

Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

PubMed

Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-03-21

Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

The National Lung Screening Trial: overview and study design.

PubMed

Aberle, Denise R; Berg, Christine D; Black, William C; Church, Timothy R; Fagerstrom, Richard M; Galen, Barbara; Gareen, Ilana F; Gatsonis, Constantine; Goldin, Jonathan; Gohagan, John K; Hillman, Bruce; Jaffe, Carl; Kramer, Barnett S; Lynch, David; Marcus, Pamela M; Schnall, Mitchell; Sullivan, Daniel C; Sullivan, Dorothy; Zylak, Carl J

2011-01-01

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented. © RSNA, 2010

Effects of Pharmacokinetic Processes and Varied Dosing Schedules on the Dynamics of Acquired Resistance to Erlotinib in EGFR-Mutant Lung Cancer

PubMed Central

Foo, Jasmine; Chmielecki, Juliann; Pao, William; Michor, Franziska

2013-01-01

Introduction Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non–small-cell lung cancer. However, the evolution of acquired resistance because of a second-site mutation (T790M) within EGFR remains an obstacle to successful treatment. Methods We used mathematical modeling and available clinical trial data to predict how different pharmacokinetic parameters (fast versus slow metabolism) and dosing schedules (low dose versus high dose; missed doses with and without make-up doses) might affect the evolution of T790M-mediated resistance in mixed populations of tumor cells. Results We found that high-dose pulses with low-dose continuous therapy impede the development of resistance to the maximum extent, both pre- and post-emergence of resistance. The probability of resistance is greater in fast versus slow drug metabolizers, suggesting a potential mechanism, unappreciated to date, influencing acquired resistance in patients. In case of required dose modifications because of toxicity, little difference is observed in terms of efficacy and resistance dynamics between the standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed doses are expected to lead to resistance faster, even if make-up doses are attempted. Conclusions For existing and new kinase inhibitors, this novel framework can be used to rationally and rapidly design optimal dosing strategies to minimize the development of acquired resistance. PMID:22982659

Is it useful to combine sputum cytology and low-dose spiral computed tomography for early detection of lung cancer in formerly asbestos-exposed power industry workers?

PubMed Central

2014-01-01

Background Low-dose spiral computed tomography (LDSCT) in comparison to conventional chest X-ray proved to be a highly sensitive method of diagnosing early stage lung cancer. However, centrally located early stage lung tumours remain a diagnostic challenge. We determined the practicability and efficacy of early detection of lung cancer when combining LDSCT and sputum cytology. Methods Of a cohort of 4446 formerly asbestos exposed power industry workers, we examined a subgroup of 187 (4.2%) high risk participants for lung cancer at least once with both LDSCT and sputum cytology. After the examination period the participants were followed-up for more than three years. Results The examinations resulted in the diagnosis of lung cancer in 12 participants (6.4%). Six were in clinical stage I. We found 10 non-small cell lung carcinomas and one small cell lung carcinoma. Sputum specimens showed suspicious pathological findings in seven cases and in 11 cases the results of LDSCT indicated malignancies. The overall sensitivity and specificity of sputum cytology was 58.0% and 98% with positive (PPV) and negative (NPV) predictive values of 70% and 97%. For LDSCT we calculated the sensitivity and specificity of 92% and 97%. The PPV and NPV were 65% and 99% respectively. Conclusions Our results confirmed that in surveillance programmes a combination of sputum cytology and LDSCT is well feasible and accepted by the participants. Sputum examination alone is not effective enough for the detection of lung cancer, especially at early stage. Even in well- defined risk groups highly exposed to asbestos, we cannot recommend the use of combined LDSCT and sputum cytology examinations as long as no survival benefit has been proved for the combination of both methods. For ensuring low rates of false-positive and false-negative results, programme planners must closely cooperate with experienced medical practitioners and pathologists in a well-functioning interdisciplinary network. PMID:24739456

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

Pokhrel, D; Badkul, R; Jiang, H

Purpose: To compare dose distributions calculated using the iPlan XVMC algorithm and heterogeneities corrected/uncorrected Pencil Beam (PB-hete/PB-homo) algorithms for SBRT treatments of lung tumors. Methods: Ten patients with centrally located solitary lung tumors were treated using MC-based SBRT to 60Gy in 5 fractions for PTVV100%=95%. ITV was delineated on MIP-images based on 4D-CT scans. PTVs(ITV+5mm margins) ranged from 10.1–106.5cc(mean=48.6cc). MC-SBRT plans were generated with a combination of non-coplanar conformal arcs/beams using iPlan-XVMC-algorithm (BrainLABiPlan ver.4.1.2) for Novalis-TX consisting of HD-MLCs and 6MV-SRS(1000MU/min) mode, following RTOG 0813 dosimetric criteria. For comparison, PB-hete/PB-homo algorithms were used to re-calculate dose distributions using same beammore » configurations, MLCs/monitor units. Plans were evaluated with isocenter/maximal/mean doses to PTV. Normal lung doses were evaluated with V5/V10/V20 and mean-lung-dose(MLD), excluding PTV. Other OAR doses such as maximal spinal cord/2cc-esophagus/max bronchial tree (BT/maximal heart doses were tabulated. Results: Maximal/mean/isocenter doses to PTV calculated by PB-hete were uniformly larger than MC plans by a factors of 1.09/1.13/1.07, on average, whereas they were consistently lower by PB-homo by a factors of 0.9/0.84/0.9, respectively. The volume covered by 5Gy/10Gy/20Gy isodose-lines of the lung were comparable (average within±3%) when calculated by PB-hete compared to XVMC, but, consistently lower by PB-homo by a factors of 0.90/0.88/0.85, respectively. MLD was higher with PB-hete by 1.05, but, lower by PB-homo by 0.9, on average, compared to XVMC. XVMC max-cord/max-BT/max-heart and 2cc of esophagus doses were comparable to PB-hete; however, PB-homo underestimates by a factors of 0.82/0.89/0.88/0.86, on average, respectively. Conclusion: PB-hete significantly overestimates dose to PTV relative to XVMC -hence underdosing the target. MC is more complex and accurate with tissue-heterogeneities.The magnitude of variation significantly varies with ‘small-island-tumor’ surrounded by low-density lung tissues -PB algorithms lacks later electron scattering. Dose calculation with XVMC for lung SBRT is routinely performed in our clinic, its performance for head'neck/sinus cases will also be investigated.« less

Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

PubMed Central

Botelho, Danielle; Leo, Bey F.; Massa, Christopher; Sarkar, Srijata; Tetley, Terry; Chung, Kian F.; Chen, Shu; Ryan, Mary P.; Porter, Alexandra; Atochina-Vasserman, Elena N.; Zhang, Junfeng; Schwander, Stephan; Gow, Andrew J.

2018-01-01

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function. PMID:29632485

Fast tomosynthesis for lung cancer detection using the SBDX geometry

NASA Astrophysics Data System (ADS)

Fahrig, Rebecca; Pineda, Angel R.; Solomon, Edward G.; Leung, Ann N.; Pelc, Norbert J.

2003-06-01

Radiology-based lung-cancer detection is a high-contrast imaging task, consisting of the detection of a small mass of tissue within much lower density lung parenchyma. This imaging task requires removal of confounding image details, fast image acquisition (< 0.1 s for pericardial region), low dose (comparable to a chest x-ray), high resolution (< 0.25 mm in-plane) and patient positioning flexibility. We present an investigation of tomosynthesis, implemented using the Scanning-Beam Digital X-ray System (SBDX), to achieve these goals. We designed an image-based computer model of tomosynthesis using a high-resolution (0.15-mm isotropic voxels), low-noise CT volume image of a lung phantom, numerically added spherical lesions and convolution-based tomographic blurring. Lesion visibility was examined as a function of half-tomographic angle for 2.5 and 4.0 mm diameter lesions. Gaussian distributed noise was added to the projected images. For lesions 2.5 mm and 4.0 mm in diameter, half-tomographic angles of at least 6° and 9° respectively were necessary before visualization of the lesions improved. The addition of noise for a dose equivalent to 1/10 that used for a standard chest radiograph did not significantly impair lesion detection. The results are promising, indicating that lung-cancer detection using a modified SBDX system is possible.

Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

PubMed Central

Cooper, Andrea M.; Pearl, John E.; Brooks, Jason V.; Ehlers, Stefan; Orme, Ian M.

2000-01-01

The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene. PMID:11083808

Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.

PubMed

Khoo, Bee Luan; Warkiani, Majid Ebrahimi; Tan, Daniel Shao-Weng; Bhagat, Ali Asgar S; Irwin, Darryl; Lau, Dawn Pingxi; Lim, Alvin S T; Lim, Kiat Hon; Krisna, Sai Sakktee; Lim, Wan-Teck; Yap, Yoon Sim; Lee, Soo Chin; Soo, Ross A; Han, Jongyoon; Lim, Chwee Teck

2014-01-01

Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.

A randomized controlled trial on the efficacy of thoracic CT screening for lung cancer in non-smokers and smokers of <30 pack-years aged 50-64 years (JECS study): research design.

PubMed

Sagawa, Motoyasu; Nakayama, Tomio; Tanaka, Makoto; Sakuma, Tsutomu; Sobue, Tomotaka

2012-12-01

In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

PubMed Central

Mesnage, Robin; Renney, George; Séralini, Gilles-Eric; Ward, Malcolm; Antoniou, Michael N.

2017-01-01

The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure. PMID:28067231

Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles

PubMed Central

2013-01-01

Purpose: Cells of the lung are at risk from exposure to low and moderate doses of ionizing radiation from a range of environmental and medical sources. To help assess human health risks from such exposures, a better understanding of the frequency and types of chromosome aberration initially-induced in human lung cell types is required to link initial DNA damage and rearrangements with transmission potential and, to assess how this varies with radiation quality. Materials and methods: We exposed normal human bronchial lung epithelial (NHBE) cells in vitro to 0.5 and 1 Gy low-linear energy transfer (LET) γ-rays and a low fluence of high-LET α-particles and assayed for chromosome aberrations in premature chromosome condensation (PCC) spreads by 24-color multiplex-fluorescence in situ hybridization (M-FISH). Results: Both simple and complex aberrations were induced in a LET and dose-dependent manner; however, the frequency and complexity observed were reduced in comparison to that previously reported in spherical cell types after exposure to comparable doses or fluence of radiation. Approximately 1–2% of all exposed cells were categorized as being capable of transmitting radiation-induced chromosomal damage to future NHBE cell generations, irrespective of dose. Conclusion: One possible mechanistic explanation for this reduced complexity is the differing geometric organization of chromosome territories within ellipsoid nuclei compared to spherical nuclei. This study highlights the need to better understand the role of nuclear organization in the formation of exchange aberrations and, the influence three-dimensional (3D) tissue architecture may have on this in vivo. PMID:23679558

Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats.

PubMed

Pineda-Farias, Jorge B; Caram-Salas, Nadia L; Salinas-Abarca, Ana B; Ocampo, Jorge; Granados-Soto, Vinicio

2017-12-01

Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED 50  = 2.79 ± 0.16 mg/kg) or gabapentin (ED 50  = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED 50  = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Low incidence of chest wall pain with a risk-adapted lung stereotactic body radiation therapy approach using three or five fractions based on chest wall dosimetry.

PubMed

Coroller, Thibaud P; Mak, Raymond H; Lewis, John H; Baldini, Elizabeth H; Chen, Aileen B; Colson, Yolonda L; Hacker, Fred L; Hermann, Gretchen; Kozono, David; Mannarino, Edward; Molodowitch, Christina; Wee, Jon O; Sher, David J; Killoran, Joseph H

2014-01-01

To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme. We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10-12 Gy×5 fractions (50-60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression. With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis. Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.

Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

PubMed

Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

2017-11-01

It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P < 0.05). There were no significant differences between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans with inhomogeneous target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

DOSE-RESPONSE RELATIONSHIPS FOR MOLECULAR ALTERATIONS INDUCED BY B[ A ]P IN STRAIN A/J MOUSE LUNG

EPA Science Inventory

Benzo[a]pyrene (B[a]P) induces tumors in rodents at doses much higher than those found in the environment. Current cancer risk assessment of B[a]P assumes that the risk posed by low level exposure to B[a]P is linear with respect to dose. We have measur...

Using patient data similarities to predict radiation pneumonitis via a self-organizing map

NASA Astrophysics Data System (ADS)

Chen, Shifeng; Zhou, Sumin; Yin, Fang-Fang; Marks, Lawrence B.; Das, Shiva K.

2008-01-01

This work investigates the use of the self-organizing map (SOM) technique for predicting lung radiation pneumonitis (RP) risk. SOM is an effective method for projecting and visualizing high-dimensional data in a low-dimensional space (map). By projecting patients with similar data (dose and non-dose factors) onto the same region of the map, commonalities in their outcomes can be visualized and categorized. Once built, the SOM may be used to predict pneumonitis risk by identifying the region of the map that is most similar to a patient's characteristics. Two SOM models were developed from a database of 219 lung cancer patients treated with radiation therapy (34 clinically diagnosed with Grade 2+ pneumonitis). The models were: SOMall built from all dose and non-dose factors and, for comparison, SOMdose built from dose factors alone. Both models were tested using ten-fold cross validation and Receiver Operating Characteristics (ROC) analysis. Models SOMall and SOMdose yielded ten-fold cross-validated ROC areas of 0.73 (sensitivity/specificity = 71%/68%) and 0.67 (sensitivity/specificity = 63%/66%), respectively. The significant difference between the cross-validated ROC areas of these two models (p < 0.05) implies that non-dose features add important information toward predicting RP risk. Among the input features selected by model SOMall, the two with highest impact for increasing RP risk were: (a) higher mean lung dose and (b) chemotherapy prior to radiation therapy. The SOM model developed here may not be extrapolated to treatment techniques outside that used in our database, such as several-field lung intensity modulated radiation therapy or gated radiation therapy.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

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

Cadena, M. S. Reyes; Chapul, L. Sanchez; Perez, Javier

2008-08-11

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-{beta}) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animalsmore » subjected to ELF together with the transfer factor.« less

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry.

PubMed

Sun, Xiaowei; Xu, Wei; Zeng, Yan; Hou, Yurong; Guo, Lin; Zhao, Xiujuan; Sun, Changhao

2014-02-01

The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry. Copyright © 2012 John Wiley & Sons, Ltd.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

PubMed

Schneer, Sonia; Kramer, Mordechai R; Fox, Benjamin; Rusanov, Viktoria; Fruchter, Oren; Rosengarten, Dror; Bakal, Ilana; Medalion, Benjamin; Raviv, Yael

2014-06-01

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects on lung stress of position and different doses of perfluorocarbon in a model of ARDS.

PubMed

López-Aguilar, Josefina; Lucangelo, Umberto; Albaiceta, Guillermo M; Nahum, Avi; Murias, Gastón; Cañizares, Rosario; Oliva, Joan Carles; Romero, Pablo V; Blanch, Lluís

2015-05-01

We determined whether the combination of low dose partial liquid ventilation (PLV) with perfluorocarbons (PFC) and prone positioning improved lung function while inducing minimal stress. Eighteen pigs with acute lung injury were assigned to conventional mechanical ventilation (CMV) or PLV (5 or 10 ml/kg of PFC). Positive end-expiratory pressure (PEEP) trials in supine and prone positions were performed. Data were analyzed by a multivariate polynomial regression model. The interplay between PLV and position depended on the PEEP level. In supine PLV dampened the stress induced by increased PEEP during the trial. The PFC dose of 5 ml/kg was more effective than the dose 10 ml/kg. This effect was not observed in prone. Oxygenation was significantly higher in prone than in supine position mainly at lower levels of PEEP. In conclusion, MV settings should take both gas exchange and stress/strain into account. When protective CMV fails, rescue strategies combining prone positioning and PLV with optimal PEEP should improve gas exchange with minimal stress. Copyright © 2015 Elsevier B.V. All rights reserved.

SU-F-T-415: Differences in Lung Sparing in Deep Inspiration Breath-Hold and Free Breathing Breast Plans Calculated in Pinnacle and Monaco

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

Saenz, D; Stathakis, S

Purpose: Deep inspiration breath-hold (DIBH) is used for left-sided breast radiotherapy to spare the heart and lung. The magnitude of sparing has been shown to be significant. Monte Carlo, furthermore, has the potential to calculate most accurately the dose in the heterogeneous lung medium at the interface with the lung wall. The lung dose was investigated in Monaco to determine the level of sparing relative to that calculated in Pinnacle{sup 3}. Methods: Five patients undergoing DIBH radiotherapy on an Elekta Versa HD linear accelerator in conjunction with the Catalyst C-RAD surface imaging system were planned using Phillips Pinnacle{sup 3}. Freemore » breathing plans were also created to clinically assure a benefit. Both plans were re-calculated in Monaco to determine if there were any significant differences. The mean heart dose, mean left lung, and mean total lung dose were compared in addition to the V20 for left and both lungs. Dose was calculated as dose to medium as well as dose to water with a statistical precision of 0.7%. Results: Mean lung dose was significantly different (p < 0.003) between the two calculations for both DIBH (11.6% higher in Monaco) and free breathing (14.2% higher in Monaco). V20 was also higher in Monaco (p < 0.05) for DIBH (5.7% higher) and free breathing (4.9% higher). The mean heart dose was not significantly different between the dose calculations for either DIBH or free breathing. Results were no more than 0.1% different when calculated as dose to water. Conclusion: The use of Monte Carlo can provide insight on the lung dose for both free breathing and DIBH techniques for whole breast irradiation. While the sparing (dose reductions with DIBH as compared to free breathing) is equivalent for either planning system, the lung doses themselves are higher when calculated with Monaco.« less

Marijuana and lung diseases.

PubMed

Joshi, Manish; Joshi, Anita; Bartter, Thaddeus

2014-03-01

Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

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.

Pediatric dosimetry for intrapleural lung injections of 32P chromic phosphate

NASA Astrophysics Data System (ADS)

Konijnenberg, Mark W.; Olch, Arthur

2010-10-01

Intracavitary injections of 32P chromic phosphate are used in the therapy of pleuropulmonary blastoma and pulmonary sarcomas in children. The lung dose, however, has never been calculated despite the potential risk of lung toxicity from treatment. In this work the dosimetry has been calculated in target tissue and lung for pediatric phantoms. Pleural cavities were modeled in the Monte Carlo code MCNP within the pediatric MIRD phantoms. Both the depth-dose curves in the pleural lining and into the lung as well as 3D dose distributions were calculated for either homogeneous or inhomogeneous 32P activity distributions. Dose-volume histograms for the lung tissue and isodose graphs were generated. The results for the 2D depth-dose curve to the pleural lining and tumor around the pleural cavity correspond well with the point kernel model-based recommendations. With a 2 mm thick pleural lining, one-third of the lung parenchyma volume gets a dose more than 30 Gy (V30) for 340 MBq 32P in a 10 year old. This is close to lung tolerance. Younger children will receive a larger dose to the lung when the lung density remains equal to the adult value; the V30 relative lung volume for a 5 year old is 35% at an activity of 256 MBq and for a 1 year old 165 MBq yields a V30 of 43%. At higher densities of the lung tissue V30 stays below 32%. All activities yield a therapeutic dose of at least 225 Gy in the pleural lining. With a more normal pleural lining thickness (0.5 mm instead of 2 mm) the injected activities will have to be reduced by a factor 5 to obtain tolerable lung doses in pediatric patients. Previous dosimetry recommendations for the adult apply well down to lung surface areas of 400 cm2. Monte Carlo dosimetry quantitates the three-dimensional dose distribution, providing a better insight into the maximum tolerable activity for this therapy.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Effective and Safe Use of Glucocorticosteroids for Rescue of Late ARDS

PubMed Central

Diana, Paolo; Money, Dustin T.; Gelvin, Michael G.

2017-01-01

We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS. PMID:28337348

Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy.

PubMed

Richman, Susan; Edusa, Valentine; Fadiel, Ahmed; Naftolin, Frederick

2006-01-01

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

Ultra low-dose CT attenuation correction in PET SPM

NASA Astrophysics Data System (ADS)

Wang, Shyh-Jen; Yang, Bang-Hung; Tsai, Chia-Jung; Yang, Ching-Ching; Lee, Jason J. S.; Wu, Tung-Hsin

2010-07-01

The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 10 4 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and normal volunteers, to work towards ALARA (as low as reasonably achievable) concept for PET SPM studies.

Inhaled Corticosteroids in Lung Diseases

PubMed Central

Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

2013-01-01

Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

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

Venkatramani, Rajkumar, E-mail: rvenkatramani@chla.usc.edu; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; Kamath, Sunil

Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The followingmore » pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.« less

Patient Perspectives on Low-Dose Computed Tomography for Lung Cancer Screening, New Mexico, 2014

PubMed Central

Sussman, Andrew L.; Murrietta, Ambroshia M.; Getrich, Christina M.; Rhyne, Robert; Crowell, Richard E.; Taylor, Kathryn L.; Reifler, Ellen J.; Wescott, Pamela H.; Saeed, Ali I.; Hoffman, Richard M.

2016-01-01

Introduction National guidelines call for annual lung cancer screening for high-risk smokers using low-dose computed tomography (LDCT). The objective of our study was to characterize patient knowledge and attitudes about lung cancer screening, smoking cessation, and shared decision making by patient and health care provider. Methods We conducted semistructured qualitative interviews with patients with histories of heavy smoking who received care at a Federally Qualified Health Center (FQHC Clinic) and at a comprehensive cancer center-affiliated chest clinic (Chest Clinic) in Albuquerque, New Mexico. The interviews, conducted from February through September 2014, focused on perceptions about health screening, knowledge and attitudes about LDCT screening, and preferences regarding decision aids. We used a systematic iterative analytic process to identify preliminary and emergent themes and to create a coding structure. Results We reached thematic saturation after 22 interviews (10 at the FQHC Clinic, 12 at the Chest Clinic). Most patients were unaware of LDCT screening for lung cancer but were receptive to the test. Some smokers said they would consider quitting smoking if their screening result were positive. Concerns regarding screening were cost, radiation exposure, and transportation issues. To support decision making, most patients said they preferred one-on-one discussions with a provider. They also valued decision support tools (print materials, videos), but raised concerns about readability and Internet access. Conclusion Implementing lung cancer screening in sociodemographically diverse populations poses significant challenges. The value of tobacco cessation counseling cannot be overemphasized. Effective interventions for shared decision making to undergo lung cancer screening will need the active engagement of health care providers and will require the use of accessible decision aids designed for people with low health literacy. PMID:27536900

Lung Cancer Screening Guidelines: How Readable Are Internet-Based Patient Education Resources?

PubMed

Hansberry, David Richard; White, Michael D; D'Angelo, Michael; Prabhu, Arpan V; Kamel, Sarah; Lakhani, Paras; Sundaram, Baskaran

2018-04-30

Following the findings of the National Lung Screening Trial, several national societies from multiple disciplines have endorsed the use of low-dose chest CT to screen for lung cancer. Online patient education materials are an important tool to disseminate information to the general public regarding the proven health benefits of lung cancer screening. This study aims to evaluate the reading level at which these materials related to lung cancer screening are written. The four terms "pulmonary nodule," "radiation," "low-dose CT," and "lung cancer screening" were searched on Google, and the first 20 online resources for each term were downloaded, converted into plain text, and analyzed using 10 well-established readability scales. If the websites were not written specifically for patients, they were excluded. The 80 articles were written at a 12.6 ± 2.7 (mean ± SD) grade level, with grade levels ranging from 4.0 to 19.0. Of the 80 articles, 62.5% required a high school education to comprehend, and 22.6% required a college degree or higher (≥ 16th grade) to comprehend. Only 2.5% of the analyzed articles adhered to the recommendations of the National Institutes of Health and American Medical Association that patient education materials be written at a 3rd- to 7th-grade reading level. Commonly visited online lung cancer screening-related patient education materials are written at a level beyond the general patient population's ability to comprehend and may be contributing to a knowledge gap that is inhibiting patients from improving their health literacy.

Imaging of Ras/Raf activity induced by low energy laser irradiation in living cell using FRET

NASA Astrophysics Data System (ADS)

Wang, Fang; Chen, Tong-Sheng; Xing, Da

2005-01-01

Ras/Raf signaling pathway is an important signaling pathway that governs cell proliferation, differential and apoptosis. Low-energy laser irradiation (LELI) was found to modulate various processes. Generally, cell proliferation is induced by low doses LELI and apoptosis is induced by high doses LELI. Mechanism of biological effect of LELI has not been clear. Recently, activation of MEK (mitogen-activated protein kinase) and ERK (extracellular-signal-regulated kinase), which are downstream protein kinases of Ras/Raf, are observed during LELI-induced cell proliferation by immunoprecipitation and western blot analysis. RaichuRas reporter consisting of fusions of H-ras, the Ras-binding domain of Raf (RafRBD), a cyan fluorescent protein (CFP) and a yellow fluorescent protein (YFP). Therefore, intramolecular binding of GTP-Ras to RafRBD brings CFP close to YFP and increases FRET between CFP and YFP. Human lung adenocarcinoma cell line (ASTC-a-1) was transfected with the plasmid (pRaichuRas) and then treated with LELI at dose of 60J/cm2. Effect of LELI on Ras/Raf in physiological condition of living cells was observed by fluorescence resonance energy transfer (FRET) technique during lung adenocarcinoma cell apoptosis induced by high dose (60J/cm2) LELI. Experimental results showed that after high dose LELI treatment, the binding of Ras and Raf decreases obviously, Ras/Raf signaling pathway deregulates and cell apoptosis occurs.

Radiology metrics for safe use and regulatory compliance with CT imaging

NASA Astrophysics Data System (ADS)

Paden, Robert; Pavlicek, William

2018-03-01

The MACRA Act creates a Merit-Based Payment System, with monitoring patient exposure from CT providing one possible quality metric for meeting merit requirements. Quality metrics are also required by The Joint Commission, ACR, and CMS as facilities are tasked to perform reviews of CT irradiation events outside of expected ranges, review protocols for appropriateness, and validate parameters for low dose lung cancer screening. In order to efficiently collect and analyze irradiation events and associated DICOM tags, all clinical CT devices were DICOM connected to a parser which extracted dose related information for storage into a database. Dose data from every exam is compared to the appropriate external standard exam type. AAPM recommended CTDIvol values for head and torso, adult and pediatrics, coronary and perfusion exams are used for this study. CT doses outside the expected range were automatically formatted into a report for analysis and review documentation. CT Technologist textual content, the reason for proceeding with an irradiation above the recommended threshold, is captured for inclusion in the follow up reviews by physics staff. The use of a knowledge based approach in labeling individual protocol and device settings is a practical solution resulting in efficiency of analysis and review. Manual methods would require approximately 150 person-hours for our facility, exclusive of travel time and independent of device availability. An efficiency of 89% time savings occurs through use of this informatics tool including a low dose CT comparison review and low dose lung cancer screening requirements set forth by CMS.

Anterior Myocardial Territory May Replace the Heart as Organ at Risk in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer

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

Tan Wenyong; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan; Liu Dong

Purpose: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. Methods and Materials: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters ofmore » dose-volume histograms were compared. Results: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). Conclusions: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.« less

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

PubMed

Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui

2016-03-08

Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling

PubMed Central

Li, Wei; Zhao, Yuguang; Wen, Xue; Liang, Xinyue; Zhang, Xiaoying; Zhou, Lei; Hu, Jifan; Niu, Chao; Tian, Huimin; Han, Fujun; Chen, Xiao; Dong, Lihua; Cai, Lu; Cui, Jiuwei

2016-01-01

Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells but not in cancer cells, suggesting its potential protection of normal tissue against damage induced by conventional radiotherapy. However, the underlying mechanisms are not well established. We addressed this in the present study by examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7 (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the initiating event in hormesis and adaptive response to LDR in HBE cells. ATM activation increased the expression of CDK4/CDK6/cyclin D1 by activating the AKT/glycogen synthase kinase (GSK)-3β signaling pathway, which stimulated HBE cell proliferation. Activation of ATM/AKT/GSK-3β signaling also increased nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to increased expression of antioxidants, which mitigated cellular damage from excessive reactive oxygen species production induced by high-dose radiation. However, these effects were not observed in A549 cells. Thus, the failure to activate these pathways in A549 cells likely explains the difference between normal and cancer cells in terms of hormesis and adaptive response to LDR. PMID:27708248

Persistent Expression Changes of Fibrosis Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

NASA Technical Reports Server (NTRS)

Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Theriot, Corey; Zalesak, Selina; Yeshitla, Samrawit; Williams, Kyle; Wu, Honglu; James, John T.

2014-01-01

The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.

Anatomical decomposition in dual energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Choi, Seungyeon; Kim, Hee-Joung

2016-03-01

Lung cancer is the leading cause of cancer death worldwide and the early diagnosis of lung cancer has recently become more important. For early screening lung cancer, computed tomography (CT) has been used as a gold standard for early diagnosis of lung cancer [1]. The major advantage of CT is that it is not susceptible to the problem of misdiagnosis caused by anatomical overlapping while CT has extremely high radiation dose and cost compared to chest radiography. Chest digital tomosynthesis (CDT) is a recently introduced new modality for lung cancer screening with relatively low radiation dose compared to CT [2] and also showing high sensitivity and specificity to prevent anatomical overlapping occurred in chest radiography. Dual energy material decomposition method has been proposed for better detection of pulmonary nodules as means of reducing the anatomical noise [3]. In this study, possibility of material decomposition in CDT was tested by simulation study and actual experiment using prototype CDT. Furthermore organ absorbed dose and effective dose were compared with single energy CDT. The Gate v6 (Geant4 application for tomographic emission), and TASMIP (Tungsten anode spectral model using the interpolating polynomial) code were used for simulation study and simulated cylinder shape phantom consisted of 4 inner beads which were filled with spine, rib, muscle and lung equivalent materials. The patient dose was estimated by PCXMC 1.5 Monte Carlo simulation tool [4]. The tomosynthesis scan was performed with a linear movement and 21 projection images were obtained over 30 degree of angular range with 1.5° degree of angular interval. The proto type CDT system has same geometry with simulation study and composed of E7869X (Toshiba, Japan) x-ray tube and FDX3543RPW (Toshiba, Japan) detector. The result images showed that reconstructed with dual energy clearly visualize lung filed by removing unnecessary bony structure. Furthermore, dual energy CDT could enhance spine bone hidden by heart effectively. The effective dose in dual energy CDT was slightly higher than single energy CDT, while only 10% of average thoracic CT [5]. Dual energy tomosynthesis is a new technique; therefore, there is little guidance for its integration into the clinical practice and this study can be used to improve diagnosis efficiency of lung field screening using CDT

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

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 possibly monitor time-course of ARDS with a lower risk of exposure to ionizing radiation. A further radiation dose reduction is associated with lower accuracy in quantitative results. PMID:24004842

Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

PubMed

Pusterla, Orso; Bauman, Grzegorz; Wielpütz, Mark O; Nyilas, Sylvia; Latzin, Philipp; Heussel, Claus P; Bieri, Oliver

2017-09-01

To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD). In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps. Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Tidal volume in acute respiratory distress syndrome: how best to select it.

PubMed

Umbrello, Michele; Marino, Antonella; Chiumello, Davide

2017-07-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO 2 R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented.

Tidal volume in acute respiratory distress syndrome: how best to select it

PubMed Central

Umbrello, Michele; Marino, Antonella

2017-01-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO2R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented. PMID:28828362

TU-G-204-09: The Effects of Reduced- Dose Lung Cancer Screening CT On Lung Nodule Detection Using a CAD Algorithm

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

Young, S; Lo, P; Kim, G

2015-06-15

Purpose: While Lung Cancer Screening CT is being performed at low doses, the purpose of this study was to investigate the effects of further reducing dose on the performance of a CAD nodule-detection algorithm. Methods: We selected 50 cases from our local database of National Lung Screening Trial (NLST) patients for which we had both the image series and the raw CT data from the original scans. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel.more » 10 of the cases had at least one nodule reported on the NLST reader forms. Based on a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, the CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST reports. Subject-level mean sensitivities and false-positive rates were calculated for each dose level. Results: The mean sensitivities of the CAD algorithm were 35% at the original dose, 20% at 50% dose, and 42.5% at 25% dose. The false-positive rates, in decreasing-dose order, were 3.7, 2.9, and 10 per case. In certain cases, particularly in larger patients, there were severe photon-starvation artifacts, especially in the apical region due to the high-attenuating shoulders. Conclusion: The detection task was challenging for the CAD algorithm at all dose levels, including the original NLST dose. However, the false-positive rate at 25% dose approximately tripled, suggesting a loss of CAD robustness somewhere between 0.5 and 1.0 mGy. NCI grant U01 CA181156 (Quantitative Imaging Network); Tobacco Related Disease Research Project grant 22RT-0131.« less

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.

Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.

PubMed

Mesnage, Robin; Arno, Matthew; Costanzo, Manuela; Malatesta, Manuela; Séralini, Gilles-Eric; Antoniou, Michael N

2015-08-25

Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from -3.5 to 3.7 fold in liver and from -4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage to tissues. Observed alterations in gene expression were consistent with fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with and thus confirm observations of pathology made at an anatomical, histological and biochemical level. Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations.

Absorbed doses of lungs from radon retained in airway lumens of mice and rats.

PubMed

Sakoda, Akihiro; Ishimori, Yuu; Yamaoka, Kiyonori; Kataoka, Takahiro; Mitsunobu, Fumihiro

2013-08-01

This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

[Regulation of the neuronal functional state by ultra low doses of different biologically active substances. Nonspecific effect ].

PubMed

Terekhova, S F; Grechenko, T N

2003-01-01

The role of biologically active substances in ultra-low doses (10(-15)-10(-27) mol/l) is discussed from the different points of view. The most detailed analysis of neurobiological effects produced by these doses can be studied on the preparate of completely isolated molluscan neurones. In this case the possibility arises to control the first modifications of action at the electrophysiological characteristics of neuronal activity. These changes of electrical activity can be regarded as a reaction to biologically active substance. The following characteristics were controlled: the level of membrane resting potential (MP), the electroexcitable membrane and pacemaker mechanism, chemical sensitivity of somatic membrane loci to neurotransmitter acetylcholine (Ach). Several substances were used in these experiments: two kinds of synthetic antioxidant, GABA, ethanol, serotonine, DSIP (delta-sleep inducing peptide), antibiotic ruboxil, nootrop GVS-111. The isolated neurones were placed into the special chamber. All these substances (0.35 ml) were added single dosing into this chamber with living physiological solution in concentration 10(-15)-10(-27) mol/l. The results demonstrated that all substances had initiated the development of prolonged neurophysiological responses. The intensities of neuronal reactions didn't depend in contact period on the concentration and on the type of substance. It is suggested that these data reveal the existence of unknown modes of regulation of neuronal functional states and presence of hidden channel for information transfer and receiving. This different way of regulation is extremely important influence living organisms.

Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

PubMed

Meesat, Ridthee; Belmouaddine, Hakim; Allard, Jean-François; Tanguay-Renaud, Catherine; Lemay, Rosalie; Brastaviceanu, Tiberius; Tremblay, Luc; Paquette, Benoit; Wagner, J Richard; Jay-Gerin, Jean-Paul; Lepage, Martin; Huels, Michael A; Houde, Daniel

2012-09-18

Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.

Performance of two commercial electron beam algorithms over regions close to the lung-mediastinum interface, against Monte Carlo simulation and point dosimetry in virtual and anthropomorphic phantoms.

PubMed

Ojala, J; Hyödynmaa, S; Barańczyk, R; Góra, E; Waligórski, M P R

2014-03-01

Electron radiotherapy is applied to treat the chest wall close to the mediastinum. The performance of the GGPB and eMC algorithms implemented in the Varian Eclipse treatment planning system (TPS) was studied in this region for 9 and 16 MeV beams, against Monte Carlo (MC) simulations, point dosimetry in a water phantom and dose distributions calculated in virtual phantoms. For the 16 MeV beam, the accuracy of these algorithms was also compared over the lung-mediastinum interface region of an anthropomorphic phantom, against MC calculations and thermoluminescence dosimetry (TLD). In the phantom with a lung-equivalent slab the results were generally congruent, the eMC results for the 9 MeV beam slightly overestimating the lung dose, and the GGPB results for the 16 MeV beam underestimating the lung dose. Over the lung-mediastinum interface, for 9 and 16 MeV beams, the GGPB code underestimated the lung dose and overestimated the dose in water close to the lung, compared to the congruent eMC and MC results. In the anthropomorphic phantom, results of TLD measurements and MC and eMC calculations agreed, while the GGPB code underestimated the lung dose. Good agreement between TLD measurements and MC calculations attests to the accuracy of "full" MC simulations as a reference for benchmarking TPS codes. Application of the GGPB code in chest wall radiotherapy may result in significant underestimation of the lung dose and overestimation of dose to the mediastinum, affecting plan optimization over volumes close to the lung-mediastinum interface, such as the lung or heart. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Imaging interactions of metal oxide nanoparticles with macrophage cells by ultra-high resolution scanning electron microscopy techniques.

PubMed

Plascencia-Villa, Germán; Starr, Clarise R; Armstrong, Linda S; Ponce, Arturo; José-Yacamán, Miguel

2012-11-01

Use of engineered metal oxide nanoparticles in a plethora of biological applications and custom products has warned about some possible dose-dependent cytotoxic effects. Macrophages are key components of the innate immune system used to study possible toxic effects and internalization of different nanoparticulate materials. In this work, ultra-high resolution field emission scanning electron microscopy (FE-SEM) was used to offer new insights into the dynamical processes of interaction of nanomaterials with macrophage cells dosed with different concentrations of metal oxide nanoparticles (CeO(2), TiO(2) and ZnO). The versatility of FE-SEM has allowed obtaining a detailed characterization of processes of adsorption and endocytosis of nanoparticles, by using advanced analytical and imaging techniques on complete unstained uncoated cells, including secondary electron imaging, high-sensitive backscattered electron imaging, X-ray microanalysis and stereoimaging. Low voltage BF/DF-STEM confirmed nanoparticle adsorption and internalization into endosomes of CeO(2) and TiO(2), whereas ZnO develop apoptosis after 24 h of interaction caused by dissolution and invasion of cell nucleus. Ultra-high resolution scanning electron microscopy techniques provided new insights into interactions of inorganic nanoparticles with macrophage cells with high spatial resolution.

Subsolid pulmonary nodules: imaging evaluation and strategic management.

PubMed

Godoy, Myrna C B; Sabloff, Bradley; Naidich, David P

2012-07-01

Given the higher rate of malignancy of subsolid pulmonary nodules and the considerably lower growth rate of ground-glass nodules (GGNs), dedicated standardized guidelines for management of these nodules have been proposed, including long-term low-dose computed tomography (CT) follow-up (≥3 years). Physicians must be familiar with the strategic management of subsolid pulmonary nodules, and should be able to identify imaging features that suggest invasive adenocarcinoma requiring a more aggressive management. Low-dose CT screening studies for early detection of lung cancer have increased our knowledge of pulmonary nodules, and in particular our understanding of the strong although imperfect correlation of the subsolid pulmonary nodules, including pure GGNs and part-solid nodules, with the spectrum of preinvasive to invasive lung adenocarcinoma. Serial CT imaging has shown stepwise progression in a subset of these nodules, characterized by increase in size and density of pure GGNs and development of a solid component, the latter usually indicating invasive adenocarcinoma. There is close correlation between the CT features of subsolid nodules (SSNs) and the spectrum of lung adenocarcinoma. Standardized guidelines are suggested for management of SSNs.

Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

PubMed

Creaven, P J; Raghavan, D; Pendyala, L; Loewen, G; Kindler, H L; Berghorn, E J

1997-08-01

The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]). Treatment-naive patients tolerated high paclitaxel doses (270 mg/m2) with carboplatin (dosed to a target area under the curve of 4.5 mg x min x mL[-1]) without granulocyte colony-stimulating factor support. Twenty-three patients (including previously treated and untreated) with non-small cell lung cancer were entered at a variety of paclitaxel doses in the phase I studies. At 100 to 205 mg/m2 paclitaxel, none of nine treated patients responded; at 230 to 290 mg/m2, four (29%) of 14 responded. In the phase II study of paclitaxel 250 mg/m2 in previously untreated patients with small cell lung cancer, two of five evaluable patients with extensive-stage disease have shown a partial response. In a preliminary analysis of the pharmacodynamics of paclitaxel in relation to neurotoxicity (dose limiting in two of three phase I studies), neurotoxicity correlated with the total dose of paclitaxel, the area under the curve, and the peak paclitaxel concentration, but not with the length of time plasma paclitaxel levels remained above 0.05 micromol/L. These correlations were not strong, however, and analysis of these data is ongoing.

Ultra Low Outgassing silicone performance in a simulated space ionizing radiation environment

NASA Astrophysics Data System (ADS)

Velderrain, M.; Malave, V.; Taylor, E. W.

2010-09-01

The improvement of silicone-based materials used in space and aerospace environments has garnered much attention for several decades. Most recently, an Ultra Low Outgassing™ silicone incorporating innovative reinforcing and functional fillers has shown that silicone elastomers with unique and specific properties can be developed to meet applications requiring stringent outgassing requirements. This paper will report on the next crucial step in qualifying these materials for spacecraft applications requiring chemical and physical stability in the presence of ionizing radiation. As a first step in this process, selected materials were irradiated with Co-60 gamma-rays to simulate the total dose received in near- Earth orbits. The paper will present pre-and post-irradiation response data of Ultra Low Outgassing silicone samples exposed under ambient air environment coupled with measurements of collected volatile condensable material (CVCM) and total mass loss (TML) per the standard conditions in ASTM E 595. The data will show an insignificant effect on the CVCMs and TMLs after exposure to various dosages of gamma radiation. This data may favorably impact new applications for these silicone materials for use as an improved sealant for space solar cell systems, space structures, satellite systems and aerospace systems.

The Case for Lung Cancer Screening: What Nurses Need to Know.

PubMed

Sorrie, Kerrin; Cates, Lisa; Hill, Alethea

2016-06-01

Lung cancer screening with low-dose helical computed tomography (LDCT) can improve high-risk individuals' chances of being diagnosed at an earlier stage and increase survival. The aims of this article are to present the risk factors associated with the development of lung cancer, identify patients at high risk for lung cancer qualifying for LDCT screening, and understand the importance of early lung cancer detection through the use of LDCT screening. PubMed and CINAHL® databases were searched with key words lung cancer screening to identify full-text academic articles from 2004-2014. This resulted in 529 articles from PubMed and 195 from CINAHL. PubMed offered suggestions for additional relevant journal articles. The National Comprehensive Cancer Network guidelines also provided substantial evidence-based information. Nurses need to provide support, education, and resources for patients undergoing lung cancer screening.

A Randomized Trial of the Effects of Nebulized Albuterol on Pulmonary Edema in Brain Dead Organ Donors

PubMed Central

Ware, Lorraine B.; Landeck, Megan; Koyama, Tatsuki; Zhao, Zhiguo; Singer, Jonathan; Kern, Ryan; Neidlinger, Nikole; Nguyen, John; Johnson, Elizabeth; Janz, David R.; Bernard, Gordon R.; Lee, Jae W.; Matthay, Michael A.

2013-01-01

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5 mg q4h) versus saline placebo during active donor management in 506 organ donors. The primary outcome was change in oxygenation (PaO2/FiO2) from enrollment to organ procurement. The albuterol (n=260) and placebo (n=246) groups were well matched for age, gender, ethnicity, smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p=0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%, p=0.44). Donors in the albuterol vs. placebo group were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%, p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia. High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema. PMID:24730050

Dosimetric comparison between modulated arc therapy and static intensity modulated radiotherapy in thoracic esophageal cancer: a single institutional experience.

PubMed

Choi, Kyu Hye; Kim, Jina; Lee, Sea-Won; Kang, Young-Nam; Jang, HongSeok

2018-03-01

The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V 5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart V 30 (p = 0.039), V 40 (p = 0.040), and V 50 (p = 0.032). Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung V 10 , V 20 , and V 30 than in 3D-CRT, but could not be proven superior in lung V 5 . In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities.

Passive shimming of the fringe field of a superconducting magnet for ultra-low field hyperpolarized noble gas MRI.

PubMed

Parra-Robles, Juan; Cross, Albert R; Santyr, Giles E

2005-05-01

Hyperpolarized noble gases (HNGs) provide exciting possibilities for MR imaging at ultra-low magnetic field strengths (<0.15 T) due to the extremely high polarizations available from optical pumping. The fringe field of many superconductive magnets used in clinical MR imaging can provide a stable magnetic field for this purpose. In addition to offering the benefit of HNG MR imaging alongside conventional high field proton MRI, this approach offers the other useful advantage of providing different field strengths at different distances from the magnet. However, the extremely strong field gradients associated with the fringe field present a major challenge for imaging since impractically high active shim currents would be required to achieve the necessary homogeneity. In this work, a simple passive shimming method based on the placement of a small number of ferromagnetic pieces is proposed to reduce the fringe field inhomogeneities to a level that can be corrected using standard active shims. The method explicitly takes into account the strong variations of the field over the volume of the ferromagnetic pieces used to shim. The method is used to obtain spectra in the fringe field of a high-field (1.89 T) superconducting magnet from hyperpolarized 129Xe gas samples at two different ultra-low field strengths (8.5 and 17 mT). The linewidths of spectra measured from imaging phantoms (30 Hz) indicate a homogeneity sufficient for MRI of the rat lung.

DNA Damage Following Pulmonary Exposure by Instillation to Low Doses of Carbon Black (Printex 90) Nanoparticles in Mice

PubMed Central

Kyjovska, Zdenka O; Jacobsen, Nicklas R; Saber, Anne T; Bengtson, Stefan; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

2015-01-01

We previously observed genotoxic effects of carbon black nanoparticles at low doses relative to the Danish Occupational Exposure Limit (3.5 mg/m3). Furthermore, DNA damage occurred in broncho-alveolar lavage (BAL) cells in the absence of inflammation, indicating that inflammation is not required for the genotoxic effects of carbon black. In this study, we investigated inflammatory and acute phase response in addition to genotoxic effects occurring following exposure to nanoparticulate carbon black (NPCB) at even lower doses. C57BL/6JBomTac mice were examined 1, 3, and 28 days after a single instillation of 0.67, 2, 6, and 162 µg Printex 90 NPCB and vehicle. Cellular composition and protein concentration was evaluated in BAL fluid as markers of inflammatory response and cell damage. DNA strand breaks in BAL cells, lung, and liver tissue were assessed using the alkaline comet assay. The pulmonary acute phase response was analyzed by Saa3 mRNA real-time quantitative PCR. Instillation of the low doses of NPCB induced a slight neutrophil influx one day after exposure. Pulmonary exposure to small doses of NPCB caused an increase in DNA strand breaks in BAL cells and lung tissue measured using the comet assay. We interpret the increased DNA strand breaks occurring following these low exposure doses of NPCB as DNA damage caused by primary genotoxicity in the absence of substantial inflammation, cell damage, and acute phase response. Environ. Mol. Mutagen. 56:41–49, 2015. © 2014 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:25042074

SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

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

Cui, G; Shiu, A; Zhou, S

Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder formore » rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator.« less

Measurement of lung volumes from supine portable chest radiographs.

PubMed

Ries, A L; Clausen, J L; Friedman, P J

1979-12-01

Lung volumes in supine nonambulatory patients are physiological parameters often difficult to measure with current techniques (plethysmograph, gas dilution). Existing radiographic methods for measuring lung volumes require standard upright chest radiographs. Accordingly, in 31 normal supine adults, we determined helium-dilution functional residual and total lung capacities and measured planimetric lung field areas (LFA) from corresponding portable anteroposterior and lateral radiographs. Low radiation dose methods, which delivered less than 10% of that from standard portable X-ray technique, were utilized. Correlation between lung volume and radiographic LFA was highly significant (r = 0.96, SEE = 10.6%). Multiple-step regressions using height and chest diameter correction factors reduced variance, but weight and radiographic magnification factors did not. In 17 additional subjects studied for validation, the regression equations accurately predicted radiographic lung volume. Thus, this technique can provide accurate and rapid measurement of lung volume in studies involving supine patients.

Ultralow Dose MSCT Imaging in Dental Implantology

PubMed Central

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

2018-01-01

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

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

Vostrotin, Vadim; Birchall, Alan; Zhdanov, Alexey

The distribution of calculated internal doses was determined for 8043 Mayak Production Associate (Mayak PA) workers according to the epidemiological cohorts and groups of raw data used as well as the type of industrial compounds of inhaled aerosols. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185585 mGy, with a median value of 31 mGy and a maximum of 8980 mGy maximum. The ranges of relative standard uncertainty were: from 40 to 2200% for accumulated lung dose,more » from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-18% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to lognormal. The accumulated internal plutonium dose to systemic organs was close to a log-triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar-interstitial region, liver, bone surface cells and red bone marrow, calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8-13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.8 in median value, while accumulated doses to systemic organs increased by 6-12% in median value.« less

Reconstruction of Internal Doses for the Alpha-Risk Case-Control Study of Lung Cancer and Leukaemia Among European Nuclear Workers.

PubMed

Bingham, Derek; Bérard, Philippe; Birchall, Alan; Bull, Richard; Cardis, Elisabeth; Challeton-de Vathaire, Cécile; Grellier, James; Hurtgen, Christian; Puncher, Matthew; Riddell, Anthony; Thierry-Chef, Isabelle

2017-05-01

The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today. © Crown copyright 2016.

Implantable ultra-low pulmonary pressure monitoring system for fetal surgery.

PubMed

Etemadi, Mozziyar; Heller, J Alex; Schecter, Samuel C; Shue, Eveline H; Miniati, Doug; Roy, Shuvo

2012-11-01

Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this work, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H2O resolution and can record for twenty one days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown.

The effects of slice thickness and radiation dose level variations on computer-aided diagnosis (CAD) nodule detection performance in pediatric chest CT scans

NASA Astrophysics Data System (ADS)

Emaminejad, Nastaran; Lo, Pechin; Ghahremani, Shahnaz; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

2017-03-01

For pediatric oncology patients, CT scans are performed to assess treatment response and disease progression. CAD may be used to detect lung nodules which would reflect metastatic disease. The purpose of this study was to investigate the effects of reducing radiation dose and varying slice thickness on CAD performance in the detection of solid lung nodules in pediatric patients. The dataset consisted of CT scans of 58 pediatric chest cases, from which 7 cases had lung nodules detected by radiologist, and a total of 28 nodules were marked. For each case, the original raw data (sinogram data) was collected and a noise addition model was used to simulate reduced-dose scans of 50%, 25% and 10% of the original dose. In addition, the original and reduced-dose raw data were reconstructed at slice thicknesses of 1.5 and 3 mm using a medium sharp (B45) kernel; the result was eight datasets (4 dose levels x 2 thicknesses) for each case An in-house CAD tool was applied on all reconstructed scans, and results were compared with the radiologist's markings. Patient level mean sensitivities at 3mm thickness were 24%, 26%, 25%, 27%, and at 1.5 mm thickness were 23%, 29%, 35%, 36% for 10%, 25%, 50%, and 100% dose level, respectively. Mean FP numbers were 1.5, 0.9, 0.8, 0.7 at 3 mm and 11.4, 3.5, 2.8, 2.8 at 1.5 mm thickness for 10%, 25%, 50%, and 100% dose level respectively. CAD sensitivity did not change with dose level for 3mm thickness, but did change with dose for 1.5 mm. False Positives increased at low dose levels where noise values were high.

Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

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

Modh, Ankit; Rimner, Andreas; Williams, Eric

2014-12-01

Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonarymore » toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.« less

Pulmonary and hepatic lesions caused by the dehydropyrrolizidine alkaloid-producing plants Crotalaria juncea and Crotalaria retusa in donkeys.

PubMed

Pessoa, C R M; Pessoa, A F A; Maia, L A; Medeiros, R M T; Colegate, S M; Barros, S S; Soares, M P; Borges, A S; Riet-Correa, F

2013-09-01

The effects and susceptibility of donkeys to Crotalaria juncea and Crotalaria retusa poisoning were determined at high and low doses. Seeds of C. juncea containing 0.074% of dehydropyrrolizidine alkaloids (DHPAs) (isohemijunceines 0.05%, trichodesmine 0.016%, and junceine 0.008%) were administered to three donkeys at 0.3, 0.6 and 1 g/kg body weight (g/kg) daily for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was a mild liver megalocytosis in the donkeys ingesting 0.6 and 1 g/kg/day. Two other donkeys that received daily doses of 3 and 5 g seed/kg showed initial respiratory signs 70 and 40 days after the start of the administration, respectively. The donkeys were euthanized following severe respiratory signs and the main lung lesions were proliferation of Clara cells and interstitial fibrosis. Three donkeys ingested seeds of C. retusa containing 5.99% of monocrotaline at daily doses of 0.025, 0.05 and 0.1 g/kg for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was moderate liver megalocytosis in each of the three donkeys. One donkey that received a single dose of 5 g/kg of C. retusa seeds and another that received 1 g/kg daily for 7 days both showed severe clinical signs and died with diffuse centrilobular liver necrosis. No lung lesions were observed. Another donkey that received a single dose of 2.5 g/kg of C. retusa seeds showed no clinical signs. The hepatic and pneumotoxic effects observed are consistent with an etiology involving DHPAs. Furthermore, the occurrence of lung or liver lesions correlates with the type of DHPAs contained in the seeds. Similarly as has been reported for horses, the data herein suggest that in donkeys some DHPAs are metabolized in the liver causing liver disease, whereas others are metabolized in the lung by Clara cells causing lung disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

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

Jenkins, Peter, E-mail: peter.jenkins@glos.nhs.uk; Watts, Joanne

2011-07-15

Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlatedmore » with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.« less

Development and validation of automated 2D-3D bronchial airway matching to track changes in regional bronchial morphology using serial low-dose chest CT scans in children with chronic lung disease.

PubMed

Raman, Pavithra; Raman, Raghav; Newman, Beverley; Venkatraman, Raman; Raman, Bhargav; Robinson, Terry E

2010-12-01

To address potential concern for cumulative radiation exposure with serial spiral chest computed tomography (CT) scans in children with chronic lung disease, we developed an approach to match bronchial airways on low-dose spiral and low-dose high-resolution CT (HRCT) chest images to allow serial comparisons. An automated algorithm matches the position and orientation of bronchial airways obtained from HRCT slices with those in the spiral CT scan. To validate this algorithm, we compared manual matching vs automatic matching of bronchial airways in three pediatric patients. The mean absolute percentage difference between the manually matched spiral CT airway and the index HRCT airways were 9.4 ± 8.5% for the internal diameter measurements, 6.0 ± 4.1% for the outer diameter measurements, and 10.1 ± 9.3% for the wall thickness measurements. The mean absolute percentage difference between the automatically matched spiral CT airway measurements and index HRCT airway measurements were 9.2 ± 8.6% for the inner diameter, 5.8 ± 4.5% for the outer diameter, and 9.9 ± 9.5% for the wall thickness. The overall difference between manual and automated methods was 2.1 ± 1.2%, which was significantly less than the interuser variability of 5.1 ± 4.6% (p<0.05). Tests of equivalence had p<0.05, demonstrating no significant difference between the two methods. The time required for matching was significantly reduced in the automated method (p<0.01) and was as accurate as manual matching, allowing efficient comparison of airways obtained on low-dose spiral CT imaging with low-dose HRCT scans.

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

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

Liu, J; Eldib, A; Ma, C

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number wasmore » used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.« less

Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

PubMed

Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

2015-01-01

Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

The National Lung Screening Trial: Overview and Study Design1

PubMed Central

2011-01-01

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented. © RSNA, 2010 Clinical trial registration no. NCT 00047385 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10091808/-/DC1 PMID:21045183

Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

NASA Astrophysics Data System (ADS)

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

2017-03-01

A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

The effect of CT technical factors on quantification of lung fissure integrity

NASA Astrophysics Data System (ADS)

Chong, D.; Brown, M. S.; Ochs, R.; Abtin, F.; Brown, M.; Ordookhani, A.; Shaw, G.; Kim, H. J.; Gjertson, D.; Goldin, J. G.

2009-02-01

A new emphysema treatment uses endobronchial valves to perform lobar volume reduction. The degree of fissure completeness may predict treatment efficacy. This study investigated the behavior of a semiautomated algorithm for quantifying lung fissure integrity in CT with respect to reconstruction kernel and dose. Raw CT data was obtained for six asymptomatic patients from a high-risk population for lung cancer. The patients were scanned on either a Siemens Sensation 16 or 64, using a low-dose protocol of 120 kVp, 25 mAs. Images were reconstructed using kernels ranging from smooth to sharp (B10f, B30f, B50f, B70f). Research software was used to simulate an even lower-dose acquisition of 15 mAs, and images were generated at the same kernels resulting in 8 series per patient. The left major fissure was manually contoured axially at regular intervals, yielding 37 contours across all patients. These contours were read into an image analysis and pattern classification system which computed a Fissure Integrity Score (FIS) for each kernel and dose. FIS values were analyzed using a mixed-effects model with kernel and dose as fixed effects and patient as random effect to test for difference due to kernel and dose. Analysis revealed no difference in FIS between the smooth kernels (B10f, B30f) nor between sharp kernels (B50f, B70f), but there was a significant difference between the sharp and smooth groups (p = 0.020). There was no significant difference in FIS between the two low-dose reconstructions (p = 0.882). Using a cutoff of 90%, the number of incomplete fissures increased from 5 to 10 when the imaging protocol changed from B50f to B30f. Reconstruction kernel has a significant effect on quantification of fissure integrity in CT. This has potential implications when selecting patients for endobronchial valve therapy.

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

PubMed

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

2009-10-01

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

Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

NASA Astrophysics Data System (ADS)

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

2015-03-01

Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

PubMed

Guckenberger, Matthias; Klement, Rainer J; Allgäuer, Michael; Andratschke, Nicolaus; Blanck, Oliver; Boda-Heggemann, Judit; Dieckmann, Karin; Duma, Marciana; Ernst, Iris; Ganswindt, Ute; Hass, Peter; Henkenberens, Christoph; Holy, Richard; Imhoff, Detlef; Kahl, Henning K; Krempien, Robert; Lohaus, Fabian; Nestle, Ursula; Nevinny-Stickel, Meinhard; Petersen, Cordula; Semrau, Sabine; Streblow, Jan; Wendt, Thomas G; Wittig, Andrea; Flentje, Michael; Sterzing, Florian

2016-03-01

To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

PubMed

Salas, Ariel A; Smith, Kelly A; Rodgers, Mackenzie D; Phillips, Vivien; Ambalavanan, Namasivayam

2015-11-01

Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates. This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth. Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01). High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

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

Sillanpaa, Jussi; Chang Jenghwa; Mageras, Gikas

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 amore » 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.« less

Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip.

PubMed

Li, Encheng; Xu, Zhiyun; Liu, Fen; Wang, Huiling; Wen, Jiabin; Shao, Shujuan; Zhang, Lichuan; Wang, Lei; Liu, Chong; Lu, Jianxin; Wang, Wenxin; Gao, Zhancheng; Wang, Qi

2014-08-01

Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear. In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE. Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways. The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.

Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

PubMed

Chaves, Aida J; Busquets, Nuria; Campos, Naiana; Ramis, Antonio; Dolz, Roser; Rivas, Raquel; Valle, Rosa; Abad, F Xavier; Darji, Ayub; Majo, Natalia

2011-04-01

To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

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.

Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers.

PubMed

Perkins, Kenneth A; Kunkle, Nicole; Karelitz, Joshua L

2017-04-01

The lowest threshold content (or "dose") of nicotine discriminated in cigarettes may differ due to menthol preference. Menthol and non-menthol Spectrum research cigarettes differing in nicotine content were used to determine discrimination thresholds. Dependent smokers preferring menthol (n = 40) or non-menthol (n = 21) brands were tested on ability to discriminate cigarettes (matched for their menthol preference) with nicotine contents of 16-17, 11-12, 5, 2, and 1 mg/g, one per session, from an "ultra-low" cigarette with 0.4 mg/g. Controlled exposure to each cigarette was four puffs/trial, and the number of sessions was determined by the lowest nicotine content they could discriminate on >80% of trials (i.e., ≥5 of 6). We also assessed subjective perceptions and behavioral choice between cigarettes to relate them to discrimination responses. Controlling for Fagerstrom Test of Nicotine Dependence score, discrimination thresholds were more likely to be at higher nicotine content cigarettes for menthol vs. non-menthol smokers (p < .005), with medians of 16 vs. 11 mg/g, respectively. Compared to the ultra-low, threshold and subthreshold (next lowest) cigarettes differed on most perceptions and puff choice, but menthol preference did not alter these associations. Notably, threshold cigarettes did, but subthreshold did not, increase choice over the ultra-low. Threshold for discriminating nicotine via smoking may be generally higher for menthol vs. non-menthol smokers. More research is needed to identify why menthol smoking is related to higher nicotine thresholds and to verify that cigarettes unable to be discriminated do not support reinforcement.

[Detection of lung nodules. New opportunities in chest radiography].

PubMed

Pötter-Lang, S; Schalekamp, S; Schaefer-Prokop, C; Uffmann, M

2014-05-01

Chest radiography still represents the most commonly performed X-ray examination because it is readily available, requires low radiation doses and is relatively inexpensive. However, as previously published, many initially undetected lung nodules are retrospectively visible in chest radiographs. The great improvements in detector technology with the increasing dose efficiency and improved contrast resolution provide a better image quality and reduced dose needs. The dual energy acquisition technique and advanced image processing methods (e.g. digital bone subtraction and temporal subtraction) reduce the anatomical background noise by reduction of overlapping structures in chest radiography. Computer-aided detection (CAD) schemes increase the awareness of radiologists for suspicious areas. The advanced image processing methods show clear improvements for the detection of pulmonary lung nodules in chest radiography and strengthen the role of this method in comparison to 3D acquisition techniques, such as computed tomography (CT). Many of these methods will probably be integrated into standard clinical treatment in the near future. Digital software solutions offer advantages as they can be easily incorporated into radiology departments and are often more affordable as compared to hardware solutions.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

PubMed

Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

2010-09-07

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

Computer aided detection system for Osteoporosis using low dose thoracic 3D CT images

NASA Astrophysics Data System (ADS)

Tsuji, Daisuke; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Harada, Masafumi; Kusumoto, Masahiko; Tsuchida, Takaaki; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

The patient of osteoporosis is about 13 million people in Japan and it is one of healthy life problems in the aging society. It is necessary to do early stage detection and treatment in order to prevent the osteoporosis. Multi-slice CT technology has been improving the three dimensional (3D) image analysis with higher resolution and shorter scan time. The 3D image analysis of thoracic vertebra can be used for supporting to diagnosis of osteoporosis. This analysis can be used for lung cancer detection at the same time. We develop method of shape analysis and CT values of spongy bone for the detection osteoporosis. Osteoporosis and lung cancer screening show high extraction rate by the thoracic vertebral evaluation CT images. In addition, we created standard pattern of CT value per thoracic vertebra for male age group using 298 low dose data.

Study of crosslinking onset and hydrogen annealing of ultra-high molecular weight polyethylene irradiated with high-energy protons

NASA Astrophysics Data System (ADS)

Wilson, John Ford

1997-09-01

Ultra high molecular weight polyethylene (UHMW-PE) is used extensively in hip and knee endoprostheses. Radiation damage from the sterilization of these endoprostheses prior to surgical insertion results in polymer crosslinking and decreased oxidative stability. The motivation for this study was to determine if UHMW-PE could be crosslinked by low dose proton irradiation with minimal radiation damage and its subsequent deleterious effects. I found that low dose proton irradiation and post irradiation hydrogen annealing did crosslink UHMW-PE and limit post irradiation oxidation. Crosslinking onset was investigated for UHMW-PE irradiated with 2.6 and 30 MeV H+ ions at low doses from 5.7 × 1011-2.3 × 1014 ions/cm2. Crosslinking was determined from gel permeation chromatography (GPC) of 1,2,4 trichlorobenzene sol fractions and increased with dose. Fourier transform infrared spectroscopy (FTIR) showed irradiation resulted in increased free radicals confirmed from increased carbonyl groups. Radiation damage, especially at the highest doses observed, also showed up in carbon double bonds and increased methyl end groups. Hydrogen annealing after ion irradiation resulted in 40- 50% decrease in FTIR absorption associated with carbonyl. The hydrogen annealing prevented further oxidation after aging for 1024 hours at 80oC. Hydrogen annealing was successful in healing radiation damage through reacting with the free radicals generated during proton irradiation. Polyethylenes, polyesters, and polyamides are used in diverse applications by the medical profession in the treatment of orthopedic impairments and cardiovascular disease and for neural implants. These artificial implants are sterilized with gamma irradiation prior to surgery and the resulting radiation damage can lead to accelerated deterioration of the implant properties. The findings in this study will greatly impact the continued use of these materials through the elimination of many problems associated with radiation damage from sterilization. The higher energy transfer for proton compared to gamma irradiation greatly accelerated the radiation damage. Radiation damage increased linearly with dose over the range of doses examined. These results were consistent with findings from earlier researchers of gamma irradiation of polyethylene.

Sci-Thur AM: YIS – 07: Optimizing dual-energy x-ray parameters using a single filter for both high and low-energy images to enhance soft-tissue imaging

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

Bowman, Wesley; Sattarivand, Mike

Objective: To optimize dual-energy parameters of ExacTrac stereoscopic x-ray imaging system for lung SBRT patients Methods: Simulated spectra and a lung phantom were used to optimize filter material, thickness, kVps, and weighting factors to obtain bone subtracted dual-energy images. Spektr simulations were used to identify material in the atomic number (Z) range [3–83] based on a metric defined to separate spectrums of high and low energies. Both energies used the same filter due to time constraints of image acquisition in lung SBRT imaging. A lung phantom containing bone, soft tissue, and a tumor mimicking material was imaged with filter thicknessesmore » range [0–1] mm and kVp range [60–140]. A cost function based on contrast-to-noise-ratio of bone, soft tissue, and tumor, as well as image noise content, was defined to optimize filter thickness and kVp. Using the optimized parameters, dual-energy images of anthropomorphic Rando phantom were acquired and evaluated for bone subtraction. Imaging dose was measured with dual-energy technique using tin filtering. Results: Tin was the material of choice providing the best energy separation, non-toxicity, and non-reactiveness. The best soft-tissue-only image in the lung phantom was obtained using 0.3 mm tin and [140, 80] kVp pair. Dual-energy images of the Rando phantom had noticeable bone elimination when compared to no filtration. Dose was lower with tin filtering compared to no filtration. Conclusions: Dual-energy soft-tissue imaging is feasible using ExacTrac stereoscopic imaging system utilizing a single tin filter for both high and low energies and optimized acquisition parameters.« less

Possibility of using salivary ultra-weak chemiluminescence as a biomarker for feelings of anxiety in hospital settings.

PubMed

Hiramatsu, Mitsuo; Chida, Kingo; Hashimoto, Dai; Takamoto, Hisayoshi; Honzawa, Katsu; Okada, Hiroyuki; Nakamura, Kimitsugu; Takagi, Kuniaki

2016-11-01

The aim of this study was to assess whether a particular value of noninvasive salivary ultra-weak chemiluminescence (UCL) could be used as a biomarker of psychological stress. Our study covered two groups. Group 1 comprised six healthy volunteers who stayed in a hospital for one night and group 2 comprised 15 patients with lung cancer and 24 patients with respiratory diseases other than lung cancer who were in hospital for an extended stay. First, we evaluated the UCL of saliva from six healthy volunteers before and after one night in hospital. Immunoglobulin A (IgA) concentrations were also measured. The integrated intensity value of UCL was correlated with the IgA concentration (correlation coefficient 0.90). Second, in the case of a long hospital stay, we found that the maximum salivary UCL intensities were higher in patients with lung cancer than in those with respiratory diseases other than lung cancer or in 28 healthy controls. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

PubMed

Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

2013-07-21

There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. Published by Elsevier Ltd.

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

PubMed

Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Space radiation-associated lung injury in a murine model.

PubMed

Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

2015-03-01

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. Copyright © 2015 the American Physiological Society.

Ultra-low power high temperature and radiation hard complementary metal-oxide-semiconductor (CMOS) silicon-on-insulator (SOI) voltage reference.

PubMed

Boufouss, El Hafed; Francis, Laurent A; Kilchytska, Valeriya; Gérard, Pierre; Simon, Pascal; Flandre, Denis

2013-12-13

This paper presents an ultra-low power CMOS voltage reference circuit which is robust under biomedical extreme conditions, such as high temperature and high total ionized dose (TID) radiation. To achieve such performances, the voltage reference is designed in a suitable 130 nm Silicon-on-Insulator (SOI) industrial technology and is optimized to work in the subthreshold regime of the transistors. The design simulations have been performed over the temperature range of -40-200 °C and for different process corners. Robustness to radiation was simulated using custom model parameters including TID effects, such as mobilities and threshold voltages degradation. The proposed circuit has been tested up to high total radiation dose, i.e., 1 Mrad (Si) performed at three different temperatures (room temperature, 100 °C and 200 °C). The maximum drift of the reference voltage V(REF) depends on the considered temperature and on radiation dose; however, it remains lower than 10% of the mean value of 1.5 V. The typical power dissipation at 2.5 V supply voltage is about 20 μW at room temperature and only 75 μW at a high temperature of 200 °C. To understand the effects caused by the combination of high total ionizing dose and temperature on such voltage reference, the threshold voltages of the used SOI MOSFETs were extracted under different conditions. The evolution of V(REF) and power consumption with temperature and radiation dose can then be explained in terms of the different balance between fixed oxide charge and interface states build-up. The total occupied area including pad-ring is less than 0.09 mm2.

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Evaluation of MLC leaf transmission on IMRT treatment plan quality of patients with advanced lung cancer.

PubMed

Chen, Jiayun; Fu, Guishan; Li, Minghui; Song, Yixin; Dai, Jianrong; Miao, Junjie; Liu, Zhiqiang; Li, Yexiong

2017-12-14

The purpose of this paper was to evaluate the impact of leaf treatment of multileaf collimator (MLC) in plan quality of intensity-modulated radiotherapy (IMRT) of patients with advanced lung cancer. Five MLCs with different leaf transmissions (0.01%, 0.5%, 1.2%, 1.8%, and 3%) were configured for an accelerator in a treatment planning system. Correspondingly, 5 treatment plans with the same optimization setting were created and evaluated quantitatively for each patient (11 patients total) who was diagnosed with advanced lung cancer. All of the 5 plans for each patient met the dose requirement for the planning treatment volumes (PTVs) and had similar target dose homogeneity and conformity. On average, the doses to selected organs were as follows: (1) V 5 , V 20 , and the mean dose of total lung; (2) the maximum and mean dose to spinal cord planning organ-at-risk volume (PRV); and (3) V 30 and V 40 of heart, decreased slightly when MLC transmission was decreased, but with no statistical differences. There is a clear grouping of plans having total quality score (S D ) value, which is used to evaluate plan quality: (1) more than 1 (patient nos. 1 to 3, 5, and 8), and more than 2.5 (patient no. 6); (2) less than 1 (patient nos. 7 and 10); (3) around 1 (patient nos. 4, 9, and 11). As MLC transmission increased, overall S D values increased as well and plan dose requirement was harder to meet. The clinical requirements were violated increasingly as MLC transmission became large. Total S D with and without normal tissue (NT) showed similar results, with no statistically significant differences. Therefore, decrease of MLC transmission did have minimum impact on plan, and it improved target coverage and reduced normal tissue radiation slightly, with no statistical significance. Plan quality could not be significantly improved by MLC transmission reduction. However, lower MLC transmission may have advantages on lung sparing to low- and intermediate-dose exposure. Besides conventional fraction, hyperfraction, or stereotactic body radiotherapy (SBRT), the reduction on lung sparing is still essential because it is highly relevant to radiation pneumonitis (RP). It has potential to diminish incidence of RP and improve patient's quality of life after irradiation with lowered MLC transmission. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.

PubMed

Xenariou, Stefania; Liang, Hai-Dong; Griesenbach, Uta; Zhu, Jie; Farley, Raymond; Somerton, Lucinda; Singh, Charanjit; Jeffery, Peter K; Scheule, Ronald K; Cheng, Seng H; Geddes, Duncan M; Blomley, Martin; Alton, Eric W F W

2010-01-01

The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.

WE-B-207-02: CT Lung Cancer Screening and the Medical Physicist: A Dosimetry Summary of CT Participants in the National Lung Cancer Screening Trial (NLST)

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

Lee, C.

2015-06-15

The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Undermore » the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan parameters. This session will review the results and summarize the individualized doses to major organs and the mean effective dose and CTDIvol estimate for 66,157 PA chest and 23,773 CT examinations respectively, using size-dependent computational phantoms coupled with Monte Carlo calculations. Learning Objectives: Review and summarize relevant NLST findings and conclusions. Understand the scope and scale of the NLST specific to participant dosimetry. Provide a comprehensive review of NLST participant dosimetry assessments. Summarize the results of an investigation providing individualized organ dose estimates for NLST participant cohorts.« less

Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

PubMed

Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy

2015-10-15

Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays?

PubMed

Aziz, Muhammad Hammad; Schneider, Frank; Clausen, Sven; Blank, Elena; Herskind, Carsten; Afzal, Muhammad; Wenz, Frederik

2011-12-16

Radiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy). Computer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116. IORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT. The calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT.

Dosimetric effect of beam arrangement for intensity-modulated radiation therapy in the treatment of upper thoracic esophageal carcinoma

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

Fu, Yuchuan; Deng, Min; Zhou, Xiaojuan

To evaluate the lung sparing in intensity-modulated radiation therapy (IMRT) for patients with upper thoracic esophageal tumors extending inferiorly to the thorax by different beam arrangement. Overall, 15 patient cases with cancer of upper thoracic esophagus were selected for a retrospective treatment-planning study. Intensity-modulated radiation therapy plans using 4, 5, and 7 beams (4B, 5B, and 7B) were developed for each patient by direct machine parameter optimization (DMPO). All plans were evaluated with respect to dose volumes to irradiated targets and normal structures, with statistical comparisons made between 4B with 5B and 7B intensity-modulated radiation therapy plans. Differences among plansmore » were evaluated using a two-tailed Friedman test at a statistical significance of p < 0.05. The maximum dose, average dose, and the conformity index (CI) of planning target volume 1 (PTV1) were similar for 3 plans for each case. No significant difference of coverage for planning target volume 1 and maximum dose for spinal cords were observed among 3 plans in present study (p > 0.05). The average V{sub 5}, V{sub 13}, V{sub 20}, mean lung dose, and generalized equivalent uniform dose (gEUD) for the total lung were significantly lower in 4B-plans than those data in 5B-plans and 7B-plans (p < 0.01). Although the average V{sub 30} for the total lung were significantly higher in 4B-plans than those in 5B-plans and 7B-plans (p < 0.05). In addition, when comparing with the 4B-plans, the conformity/heterogeneity index of the 5B- and 7B-plans were significantly superior (p < 0.05). The 4B-intensity-modulated radiation therapy plan has advantage to address the specialized problem of lung sparing to low- and intermediate-dose exposure in the thorax when dealing with relative long tumors extended inferiorly to the thoracic esophagus for upper esophageal carcinoma with the cost for less conformity. Studies are needed to compare the superiority of volumetric modulated arc therapy with intensity-modulated radiation therapy technique.« less

SU-G-TeP1-11: Predictors of Cardiac and Lung Dose Sparing in DIBH for Left Breast Treatment

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

Cao, N; Kalet, A; Fang, L

Purpose: This retrospective study of left sided whole breast radiation therapy (RT) patients investigates possible predictive parameters correlating to cardiac and left lung dose sparing by deep inspiration breath-hold (DIBH) technique compared to free-breathing (FB). Methods: Thirty-one patients having both DIBH and FB CT scans were included in the study. All patients were planned with a standard step-and-shoot tangential technique using MV photons, with prescription of 50Gy or 50.4Gy. The displacement of the breath hold sternal mark during DIBH, the cardiac contact distances of the axial (CCDax) and parasagittal (CCDps) planes, and lateral-heart-to-chest (LHC) distance on FB CT scans weremore » measured. Lung volumes, mean dose and dose-volume histograms (V5, V10 and V20) were analyzed and compared for heart and left lung for both FB and DIBH techniques. Correlation analysis was performed to identify the predictors for heart and left lung dose sparing. Two-tailed Student’s t-test and linear regression were used for data analysis with significance level of P≤0.05. Results: All dosimetric metrics for the heart and left lung were significantly reduced (P<0.01) with DIBH. Breath hold sternal mark displacement ranged from 0.4–1.8 cm and correlated with mean (P=0.05) and V5 (P=0.02) of heart dose reduction by DIBH. FB lung volume showed correlation with mean lung dose reduction by DIBH (P<0.01). The FB-CCDps and FB-LHC distance had strong positive and negative correlation with FB mean heart dose (P<0.01) and mean heart dose reduction by DIBH (P<0.01), respectively. FB-CCDax showed no correlation with dosimetric changes. Conclusion: DIBH technique has been shown to reduce dose to the heart and left lung. In this patient cohort, FB-CCDps, FB-LHC distance, and FB lung volume served as significant predictors for heart and left lung. These parameters can be further investigated to be used as a tool to better select patients who will benefit from DIBH.« less

Comparative analysis of analgesic efficacy of selected physiotherapy methods in low back pain patients.

PubMed

Charłusz, Magdalena; Gasztych, Jowita; Irzmański, Robert; Kujawa, Jolanta

2010-01-01

Low back pain syndromes are one of the most frequent causes of movement limitation in populations of highly industrialized countries. They are listed as the main cause of inability to work among people of working age. Chronic pain and the associated limitation of movement underlie the quest for effective therapies. The use of ultrasound, LLLT, vacuum therapy with Ultra Reiz current in physical therapy of these patients prompts research over their effectiveness in the therapy of patients with low-back pain. The aim of the work was to evaluate the analgesic efficacy of LLLT, ultrasound, and vacuum therapy with Ultra Reiz current in patients with low back pain. The study involved 94 people divided into three groups (A,B,C). Group A (n=35) received a series of 10 low energy laser therapy sessions (wave length 808 nm, surface density of radiation 510 mW/cm(2), continuous wave form, scanning mode, a dose of 12 J/cm(2) on a surface of 100 cm(2) [10x10cm]). Patients in Group B (n=27) had ultrasound sessions with a wave intensity of 1 W/cm(2) for 3 minutes. Patients in Group C (n=32) underwent vacuum therapy (8 kPa) combined with Ultra Reiz current. Subjective pain assessment was carried out using a modified Latinen questionnaire and a visual analogue scale of pain intensity. Lumbosacral spine mobility was evaluated with the Schober test and the finger-to- floor test. In Group A, following low energy laser therapy, a statistically significant decrease in pain intensity was observed, together with decreased analgesic consumption compared to the other groups. In Group C, following vacuum therapy combined with Ultra Reiz currents, a significant decrease in the frequency of pain was observed together with increased physical activity compared to both Groups A and B, assessed according to a modified Laitinen pain indicator questionnaire. The biggest improvement in global spine mobility and lumbosacral flexion was observed in Group C (vacuum therapy plus Ultra Reiz current) compared to the other groups. However, the most significant improvement in lower spine extension was noted in Group B (ultrasound). 1. The study showed slightly higher analgesic efficacy of laser biostimulation in comparison to vacuum therapy combined with Ultra Reiz current in patients with low back pain. 2. A more prominent increase in lumbosacral spine mobility was observed after vacuum therapy combined with Ultra Reiz current and ultrasound therapy.

ACB-PCR MEASUREMENT OF K-RAS CODON 12 MUTATION IN A/J MOUSE LUNG EXPOSED TO BENZO[A]PYRENE: A DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a known human carcinogen and environmental contaminant. The direct measurement of K-Ras mutant fraction (MF) was developed as a metric with which to examine the default assumption of low dose linearity in the mutational response to B...

Statistical distributions of ultra-low dose CT sinograms and their fundamental limits

NASA Astrophysics Data System (ADS)

Lee, Tzu-Cheng; Zhang, Ruoqiao; Alessio, Adam M.; Fu, Lin; De Man, Bruno; Kinahan, Paul E.

2017-03-01

Low dose CT imaging is typically constrained to be diagnostic. However, there are applications for even lowerdose CT imaging, including image registration across multi-frame CT images and attenuation correction for PET/CT imaging. We define this as the ultra-low-dose (ULD) CT regime where the exposure level is a factor of 10 lower than current low-dose CT technique levels. In the ULD regime it is possible to use statistically-principled image reconstruction methods that make full use of the raw data information. Since most statistical based iterative reconstruction methods are based on the assumption of that post-log noise distribution is close to Poisson or Gaussian, our goal is to understand the statistical distribution of ULD CT data with different non-positivity correction methods, and to understand when iterative reconstruction methods may be effective in producing images that are useful for image registration or attenuation correction in PET/CT imaging. We first used phantom measurement and calibrated simulation to reveal how the noise distribution deviate from normal assumption under the ULD CT flux environment. In summary, our results indicate that there are three general regimes: (1) Diagnostic CT, where post-log data are well modeled by normal distribution. (2) Lowdose CT, where normal distribution remains a reasonable approximation and statistically-principled (post-log) methods that assume a normal distribution have an advantage. (3) An ULD regime that is photon-starved and the quadratic approximation is no longer effective. For instance, a total integral density of 4.8 (ideal pi for 24 cm of water) for 120kVp, 0.5mAs of radiation source is the maximum pi value where a definitive maximum likelihood value could be found. This leads to fundamental limits in the estimation of ULD CT data when using a standard data processing stream

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

Radiological risk assessment of Capstone depleted uranium aerosols.

PubMed

Hahn, Fletcher F; Roszell, Laurie E; Daxon, Eric G; Guilmette, Raymond A; Parkhurst, Mary Ann

2009-03-01

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models. Organs and tissues with the highest calculated committed equivalent 50-y doses were lung and extrathoracic tissues (nose and nasal passages, pharynx, larynx, mouth, and thoracic lymph nodes). Doses to the bone surface and kidney were about 5 to 10% of the doses to the extrathoracic tissues. Organ-specific risks were estimated using ICRP and U.S. Environmental Protection Agency (EPA) methodologies. Risks for crewmembers and first responders were determined for selected scenarios based on the time interval of exposure and for vehicle and armor type. The lung was the organ with the highest cancer mortality risk, accounting for about 97% of the risks summed from all organs. The highest mean lifetime risk for lung cancer for the scenario with the longest exposure time interval (2 h) was 0.42%. This risk is low compared with the natural or background risk of 7.35%. These risks can be significantly reduced by using an existing ventilation system (if operable) and by reducing personnel time in the vehicle immediately after perforation.

Using YOLO based deep learning network for real time detection and localization of lung nodules from low dose CT scans

NASA Astrophysics Data System (ADS)

Ramachandran S., Sindhu; George, Jose; Skaria, Shibon; V. V., Varun

2018-02-01

Lung cancer is the leading cause of cancer related deaths in the world. The survival rate can be improved if the presence of lung nodules are detected early. This has also led to more focus being given to computer aided detection (CAD) and diagnosis of lung nodules. The arbitrariness of shape, size and texture of lung nodules is a challenge to be faced when developing these detection systems. In the proposed work we use convolutional neural networks to learn the features for nodule detection, replacing the traditional method of handcrafting features like geometric shape or texture. Our network uses the DetectNet architecture based on YOLO (You Only Look Once) to detect the nodules in CT scans of lung. In this architecture, object detection is treated as a regression problem with a single convolutional network simultaneously predicting multiple bounding boxes and class probabilities for those boxes. By performing training using chest CT scans from Lung Image Database Consortium (LIDC), NVIDIA DIGITS and Caffe deep learning framework, we show that nodule detection using this single neural network can result in reasonably low false positive rates with high sensitivity and precision.

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

Tucker, Susan L.; Liu, H. Helen; Wang, Shulian

Purpose: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. Methods and Materials: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. Results: Normal-tissue complicationmore » probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses {>=}5 Gy (VS5), that is, exposed to doses <5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving {>=}5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, {infinity}), m = 0.55 (0.22, 1.02), and D {sub 5} = 17.5 Gy (9.4 Gy, 102 Gy). Conclusions: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving <5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of Radiation dose distribution in the lung.« less

Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

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

Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Nishibuchi, Ikuno; Murakami, Yuji

2012-03-15

Purpose: To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods and Materials: Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung.more » Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with {>=}20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. Results: V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. Conclusions: Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.« less

Dose conversion factors for radon: recent developments.

PubMed

Marsh, James W; Harrison, John D; Laurier, Dominique; Blanchardon, Eric; Paquet, François; Tirmarche, Margot

2010-10-01

Epidemiological studies of the occupational exposure of miners and domestic exposures of the public have provided strong and complementary evidence of the risks of lung cancer following inhalation of radon progeny. Recent miner epidemiological studies, which include low levels of exposure, long duration of follow-up, and good quality of individual exposure data, suggest higher risks of lung cancer per unit exposure than assumed previously by the International Commission on Radiological Protection (ICRP). Although risks can be managed by controlling exposures, dose estimates are required for the control of occupational exposures and are also useful for comparing sources of public exposure. Currently, ICRP calculates doses from radon and its progeny using dose conversion factors from exposure (WLM) to dose (mSv) based on miner epidemiological studies, referred to as the epidemiological approach. Revision of these dose conversion factors using risk estimates based on the most recent epidemiological data gives values that are in good agreement with the results of calculations using ICRP biokinetic and dosimetric models, the dosimetric approach. ICRP now proposes to treat radon progeny in the same way as other radionuclides and to publish dose coefficients calculated using models, for use within the ICRP system of protection.

Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

PubMed

Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

2006-01-01

To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose

PubMed Central

Nicolas, Fadia; Wu, Changgong; Bukhari, Salwa; de Toledo, Sonia M.; Li, Hong; Shibata, Masayuki; Azzam, Edouard I.

2015-01-01

The covalent addition of nitric oxide (NO•) onto cysteine thiols, or S-nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S-nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S-nitrosylation by the “biotin switch” assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137Cs γ rays. Analysis of modulated S-nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S-nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S-nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S-nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation. PMID:26317069

S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose.

PubMed

Nicolas, Fadia; Wu, Changgong; Bukhari, Salwa; de Toledo, Sonia M; Li, Hong; Shibata, Masayuki; Azzam, Edouard I

2015-04-28

The covalent addition of nitric oxide (NO • ) onto cysteine thiols, or S -nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S -nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S -nitrosylation by the "biotin switch" assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137 Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137 Cs γ rays. Analysis of modulated S -nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S -nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S -nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S -nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation.

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity.

PubMed

Dailey, Lea Ann; Hernández-Prieto, Raquel; Casas-Ferreira, Ana Maria; Jones, Marie-Christine; Riffo-Vasquez, Yanira; Rodríguez-Gonzalo, Encarnación; Spina, Domenico; Jones, Stuart A; Smith, Norman W; Forbes, Ben; Page, Clive; Legido-Quigley, Cristina

2015-02-01

Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p < 0.05), as well as between nanoparticles of different surface hydrophobicity (p < 0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p < 0.01), CXCL1 levels (p < 0.05) and nanoparticle surface hydrophobicity (p < 0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

Toxicity and dosimetric analysis of non-small cell lung cancer patients undergoing radiotherapy with 4DCT and image-guided intensity modulated radiotherapy: a regional centre's experience.

PubMed

Livingston, Gareth C; Last, Andrew J; Shakespeare, Thomas P; Dwyer, Patrick M; Westhuyzen, Justin; McKay, Michael J; Connors, Lisa; Leader, Stephanie; Greenham, Stuart

2016-09-01

For patients receiving radiotherapy for locally advance non-small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment-related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three-dimensional conformal radiotherapy (3DCRT). Thirty curative NSCLC patients received radiotherapy using four-dimensional computed tomography and five-field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re-planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques. IMRT plans achieved improved high-dose conformity and reduced OAR doses including lung volumes irradiated to 5-20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%. IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.

Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

PubMed

Chen, Ming-Feng; Yang, Chih-Min; Su, Cheng-Ming; Liao, Jiunn-Wang; Hu, Miao-Lin

2011-01-01

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

Impact of temporal probability in 4D dose calculation for lung tumors.

PubMed

Rouabhi, Ouided; Ma, Mingyu; Bayouth, John; Xia, Junyi

2015-11-08

The purpose of this study was to evaluate the dosimetric uncertainty in 4D dose calculation using three temporal probability distributions: uniform distribution, sinusoidal distribution, and patient-specific distribution derived from the patient respiratory trace. Temporal probability, defined as the fraction of time a patient spends in each respiratory amplitude, was evaluated in nine lung cancer patients. Four-dimensional computed tomography (4D CT), along with deformable image registration, was used to compute 4D dose incorporating the patient's respiratory motion. First, the dose of each of 10 phase CTs was computed using the same planning parameters as those used in 3D treatment planning based on the breath-hold CT. Next, deformable image registration was used to deform the dose of each phase CT to the breath-hold CT using the deformation map between the phase CT and the breath-hold CT. Finally, the 4D dose was computed by summing the deformed phase doses using their corresponding temporal probabilities. In this study, 4D dose calculated from the patient-specific temporal probability distribution was used as the ground truth. The dosimetric evaluation matrix included: 1) 3D gamma analysis, 2) mean tumor dose (MTD), 3) mean lung dose (MLD), and 4) lung V20. For seven out of nine patients, both uniform and sinusoidal temporal probability dose distributions were found to have an average gamma passing rate > 95% for both the lung and PTV regions. Compared with 4D dose calculated using the patient respiratory trace, doses using uniform and sinusoidal distribution showed a percentage difference on average of -0.1% ± 0.6% and -0.2% ± 0.4% in MTD, -0.2% ± 1.9% and -0.2% ± 1.3% in MLD, 0.09% ± 2.8% and -0.07% ± 1.8% in lung V20, -0.1% ± 2.0% and 0.08% ± 1.34% in lung V10, 0.47% ± 1.8% and 0.19% ± 1.3% in lung V5, respectively. We concluded that four-dimensional dose computed using either a uniform or sinusoidal temporal probability distribution can approximate four-dimensional dose computed using the patient-specific respiratory trace.

Expression of interferon-gamma and tumour necrosis factor-alpha messenger RNA does not correlate with protection in guinea pigs challenged with virulent Mycobacterium tuberculosis by the respiratory route.

PubMed

Jeevan, Amminikutty; Bonilla, Diana Lucia; McMurray, David Neil

2009-09-01

Cytokine messenger RNA (mRNA) expression was investigated in the spleen and lung digest cells of bacillus Calmette-Guérin (BCG)-vaccinated and non-vaccinated guinea pigs following low-dose, pulmonary exposure to virulent Mycobacterium tuberculosis. After purified protein derivative (PPD) stimulation, the levels of lung cell interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and spleen cell interleukin-12 (IL-12) p40 mRNAs were significantly increased in the non-vaccinated M. tuberculosis-infected guinea pigs compared to the BCG-vaccinated guinea pigs. In contrast, the expression of anti-inflammatory transforming growth factor-beta and IL-10 mRNAs was significantly enhanced in the spleens of BCG-vaccinated animals. Despite the presence of protective cytokine mRNA expression, the non-vaccinated guinea pigs had significantly higher lung and spleen bacterial burdens. In contrast, BCG-vaccinated guinea pigs controlled the bacterial multiplication in their lungs and spleens, indicating that both protective as well as anti-inflammatory cytokine responses are associated with a reduction in bacteria. In addition, lung digest cells from non-vaccinated guinea pigs contained a significantly higher percentage of neutrophils, CD3(+) and CD8(+) T cells, while the percentage of macrophages was increased in the BCG-vaccinated animals. Total and purified lung digest T cells co-cultured with lung macrophages (LMøs) proliferated poorly after PPD stimulation in both non-vaccinated and BCG-vaccinated animals while robust proliferation to PPD was observed when T cells were co-cultured with peritoneal macrophages (PMøs). Macrophages within the lung compartment appear to regulate the response of T cells irrespective of the vaccination status in guinea pigs. Taken together, our results suggest that type I cytokine mRNA expression is not associated with vaccine-induced protection in the low-dose guinea pig model of tuberculosis.

Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung.

PubMed

Dolovich, M A

2000-06-01

A number of studies in the literature support the use of fine aerosols of drug, inhaled at low IFRs to target peripheral airways, with the objective of improving clinical responses to inhaled therapy (Fig. 8). Attempts have been made to separate response due to changes in total administered dose or the surface concentration of the dose from response due to changes in site of deposition--both are affected by the particle size of the aerosol, with IFR additionally influencing the latter. The tools for measuring dose and distribution have improved over the last 10-15 years, and thus we should expect greater accuracy in these measurements for assessing drug delivery to the lung. There are still issues, though, in producing radiolabeled (99m)technetium aerosols that are precise markers for the pharmaceutical product being tested and in quantitating absolute doses deposited in the lung. PET isotopes may provide the means for directly labelling a drug and perhaps can offer an alternative for making these measurements in the future, but deposition measurements should not be used in isolation; protocols should incorporate clinical tests to provide parallel therapeutic data in response to inhalation of the drug by the various patient populations being studied.

Implant breast reconstruction followed by radiotherapy: Can helical tomotherapy become a standard irradiation treatment?

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

Massabeau, Carole, E-mail: cmassabeau@hotmail.com; Fournier-Bidoz, Nathalie; Wakil, Georges

2012-01-01

To evaluate the benefits and limitations of helical tomotherapy (HT) for loco-regional irradiation of patients after a mastectomy and immediate implant-based reconstruction. Ten breast cancer patients with retropectoral implants were randomly selected for this comparative study. Planning target volumes (PTVs) 1 (the volume between the skin and the implant, plus margin) and 2 (supraclavicular, infraclavicular, and internal mammary nodes, plus margin) were 50 Gy in 25 fractions using a standard technique and HT. The extracted dosimetric data were compared using a 2-tailed Wilcoxon matched-pair signed-rank test. Doses for PTV1 and PTV2 were significantly higher with HT (V95 of 98.91 andmore » 97.91%, respectively) compared with the standard technique (77.46 and 72.91%, respectively). Similarly, the indexes of homogeneity were significantly greater with HT (p = 0.002). HT reduced ipsilateral lung volume that received {>=}20 Gy (16.7 vs. 35%), and bilateral lungs (p = 0.01) and neighboring organs received doses that remained well below tolerance levels. The heart volume, which received 25 Gy, was negligible with both techniques. HT can achieve full target coverage while decreasing high doses to the heart and ipsilateral lung. However, the low doses to normal tissue volumes need to be reduced in future studies.« less

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

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

Webster, E.W.

1992-01-01

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

Effects of low-dose radiation - a correlation study.

PubMed

Edling, C; Comba, P; Axelson, O; Flodin, U

1982-01-01

The effects of low-dose radiation have been a matter of controversy over the years, and the epidemiologic results have been conflicting. A couple of recent studies have indicated a possible impact on lung cancer mortality from exposure to indoor levels of radon and radon daughters. In this study, selected mortality rates, ie, lung cancer, pancreatic cancer, breast cancer (females only), leukemia, and multiple myeloma were correlated for the counties of Sweden with estimates of average background radiation exposure in these areas. Significant correlations were obtained for lung cancer (males, r = 0.46; females r = 0.55) and pancreatic cancer (males, r = 0.59; females, r = 0.40) , and there was a borderline correlation (r = 0.36; p = 0.04) for leukemia in males. In all, there were positive correlations for eight out of the nine computations made. Since background radiation correlates with urbanization and therefore with smoking, air pollution, etc, the correlations might be spurious due to confounding; on the other hand confounding is a reciprocal phenomenon which suggests that background radiation should to be taken into consideration when widespread risk factors like smoking, coffee drinking, general air pollution, etc, are studied.

Dose profiles for lung and breast regions at prospective and retrospective CT coronary angiography using optically stimulated luminescence dosimeters on a 64-detector CT scanner.

PubMed

Funama, Yoshinori; Taguchi, Katsuyuki; Utsunomiya, Daisuke; Oda, Seitaro; Murasaki, Hiroo; Yamashita, Yasuyuki; Awai, Kazuo

2012-01-01

The purpose of our study was to acquire dose profiles at critical organs of lung and breast regions using optically stimulated luminescence (OSL) dosimeters; assess the actual radiation dose delivered at retrospective and prospective computed tomography coronary angiography (CTCA). Using a chest CT phantom we applied a prospectively-gated step-and-shoot- and a retrospectively-gated helical mode on a 64-detector row CT scanner. Retrospective scan mode was used with and without electrocardiogram (ECG) based tube current modulation. OSL dosimeters were used to measure dose profiles. In the both scan modes we acquired dose profiles and determined the mean and maximum dose in left lung and in left breast regions. In prospective mode, the mean dose was 21.53 mGy in left lung- and 23.59 mGy in left breast region. With respect to the retrospective mode, the mean dose with tube current modulation was 38.63 mGy for left lung- and 46.02 mGy for left breast region, i.e. 0.56 and 0.55 times lower than the mean dose without modulation. The OSL dosimeter is useful for measurement of the actual radiation dose along z-axis at lung and breast regions in the prospective and the retrospective CTCA. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Stereotactic, Single-Dose Irradiation of Lung Tumors: A Comparison of Absolute Dose and Dose Distribution Between Pencil Beam and Monte Carlo Algorithms Based on Actual Patient CT Scans

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

Chen Huixiao; Lohr, Frank; Fritz, Peter

2010-11-01

Purpose: Dose calculation based on pencil beam (PB) algorithms has its shortcomings predicting dose in tissue heterogeneities. The aim of this study was to compare dose distributions of clinically applied non-intensity-modulated radiotherapy 15-MV plans for stereotactic body radiotherapy between voxel Monte Carlo (XVMC) calculation and PB calculation for lung lesions. Methods and Materials: To validate XVMC, one treatment plan was verified in an inhomogeneous thorax phantom with EDR2 film (Eastman Kodak, Rochester, NY). Both measured and calculated (PB and XVMC) dose distributions were compared regarding profiles and isodoses. Then, 35 lung plans originally created for clinical treatment by PB calculationmore » with the Eclipse planning system (Varian Medical Systems, Palo Alto, CA) were recalculated by XVMC (investigational implementation in PrecisePLAN [Elekta AB, Stockholm, Sweden]). Clinically relevant dose-volume parameters for target and lung tissue were compared and analyzed statistically. Results: The XVMC calculation agreed well with film measurements (<1% difference in lateral profile), whereas the deviation between PB calculation and film measurements was up to +15%. On analysis of 35 clinical cases, the mean dose, minimal dose and coverage dose value for 95% volume of gross tumor volume were 1.14 {+-} 1.72 Gy, 1.68 {+-} 1.47 Gy, and 1.24 {+-} 1.04 Gy lower by XVMC compared with PB, respectively (prescription dose, 30 Gy). The volume covered by the 9 Gy isodose of lung was 2.73% {+-} 3.12% higher when calculated by XVMC compared with PB. The largest differences were observed for small lesions circumferentially encompassed by lung tissue. Conclusions: Pencil beam dose calculation overestimates dose to the tumor and underestimates lung volumes exposed to a given dose consistently for 15-MV photons. The degree of difference between XVMC and PB is tumor size and location dependent. Therefore XVMC calculation is helpful to further optimize treatment planning.« less

Improved Classification of Lung Cancer Using Radial Basis Function Neural Network with Affine Transforms of Voss Representation.

PubMed

Adetiba, Emmanuel; Olugbara, Oludayo O

2015-01-01

Lung cancer is one of the diseases responsible for a large number of cancer related death cases worldwide. The recommended standard for screening and early detection of lung cancer is the low dose computed tomography. However, many patients diagnosed die within one year, which makes it essential to find alternative approaches for screening and early detection of lung cancer. We present computational methods that can be implemented in a functional multi-genomic system for classification, screening and early detection of lung cancer victims. Samples of top ten biomarker genes previously reported to have the highest frequency of lung cancer mutations and sequences of normal biomarker genes were respectively collected from the COSMIC and NCBI databases to validate the computational methods. Experiments were performed based on the combinations of Z-curve and tetrahedron affine transforms, Histogram of Oriented Gradient (HOG), Multilayer perceptron and Gaussian Radial Basis Function (RBF) neural networks to obtain an appropriate combination of computational methods to achieve improved classification of lung cancer biomarker genes. Results show that a combination of affine transforms of Voss representation, HOG genomic features and Gaussian RBF neural network perceptibly improves classification accuracy, specificity and sensitivity of lung cancer biomarker genes as well as achieving low mean square error.

Imaging interactions of metal oxide nanoparticles with macrophage cells by ultra-high resolution scanning electron microscopy techniques†

PubMed Central

Plascencia-Villa, Germán; Starr, Clarise R.; Armstrong, Linda S.; Ponce, Arturo

2016-01-01

Use of engineered metal oxide nanoparticles in a plethora of biological applications and custom products has warned about some possible dose-dependent cytotoxic effects. Macrophages are key components of the innate immune system used to study possible toxic effects and internalization of different nanoparticulate materials. In this work, ultra-high resolution field emission scanning electron microscopy (FE-SEM) was used to offer new insights into the dynamical processes of interaction of nanomaterials with macrophage cells dosed with different concentrations of metal oxide nanoparticles (CeO2, TiO2 and ZnO). The versatility of FE-SEM has allowed obtaining a detailed characterization of processes of adsorption and endocytosis of nanoparticles, by using advanced analytical and imaging techniques on complete unstained uncoated cells, including secondary electron imaging, high-sensitive backscattered electron imaging, X-ray microanalysis and stereoimaging. Low voltage BF/DF-STEM confirmed nanoparticle adsorption and internalization into endosomes of CeO2 and TiO2, whereas ZnO develop apoptosis after 24 h of interaction caused by dissolution and invasion of cell nucleus. Ultra-high resolution scanning electron microscopy techniques provided new insights into interactions of inorganic nanoparticles with macrophage cells with high spatial resolution. PMID:23023106

Lung cancer mortality among workers at a nuclear materials fabrication plant.

PubMed

Richardson, David B; Wing, Steve

2006-02-01

The Oak Ridge, Tennessee Y-12 plant has operated as a nuclear materials fabrication plant since the 1940s. Given the work environment, and prior findings that lung cancer mortality was elevated among white male Y-12 workers relative to US white males, we investigated whether lung cancer mortality was associated with occupational radiation exposures. A cohort of 3,864 workers hired between 1947 and 1974 who had been monitored for internal radiation exposure was identified. Vital status was ascertained through 1990. Over the study period 111 lung cancer deaths were observed. Cumulative external radiation dose under a 5-year lag assumption was positively associated with lung cancer mortality (0.54% increase in lung cancer mortality per 10 mSv, se=0.16, likelihood ratio test (LRT)=5.84, 1 degree of freedom [df]); cumulative internal radiation dose exhibited a highly-imprecise negative association with lung cancer mortality. The positive association between external radiation dose and lung cancer mortality was primarily due to exposure occurring in the period 5-14 years after exposure (0.97% increase in lung cancer mortality rate per 10 mSv, se=0.28, LRT=6.35, 1 df). The association between external radiation dose and lung cancer mortality was negative for exposures occurring at ages<35 years and positive for exposures occurring at ages 35-50 and 50+years. There is evidence of a positive association between cumulative external radiation dose and lung cancer mortality in this population. However, a causal interpretation of this association is constrained by the uncertainties in external and internal radiation dose estimates, the lack of information about exposures to other lung carcinogens, and the limited statistical power of the study. Copyright (c) 2005 Wiley-Liss, Inc.

[The study of the role of the water medium in the mechanism of action of peptides in low and ultra low doses].

PubMed

Grigor'ev, E I; Khavinson, V Kh; Malinin, V V; Grigor'ev, A E; Kochnev, I N; Kudriavtseva, T A

2003-01-01

The correlation between the structures and conformations of short peptides KE, EW, AEDG and other, their influence on the dynamic properties of water and dose/biologic effect dependencies in a wide range of concentrations were regarded. Their effects on the dynamic properties of water were studied by temperature dependencies (5-45 degrees C) of infrared spectra of the solutions in the near (5180 cm-1) and far (200 cm-1). In vitro biotesting included the determination of the proliferative activity of thymocytes, a bimodal curve with the second maximum were detected at super-low doses (10(-17)-10(-15) mol/l). Authors propose a hypothesis that for superlow concentrations the formation and distance transmission of a signal from ligand to a target cell without the formation of any ligand-receptor complex take place. An active role in this model belongs to water medium acting according to the solution mechanism.

Attitudes and Beliefs of Primary Care Providers in New Mexico About Lung Cancer Screening Using Low-Dose Computed Tomography

PubMed Central

Hoffman, Richard M.; Sussman, Andrew L.; Getrich, Christina M.; Rhyne, Robert L.; Crowell, Richard E.; Taylor, Kathryn L.; Reifler, Ellen J.; Wescott, Pamela H.; Murrietta, Ambroshia M.; Saeed, Ali I.

2015-01-01

Introduction On the basis of results from the National Lung Screening Trial (NLST), national guidelines now recommend using low-dose computed tomography (LDCT) to screen high-risk smokers for lung cancer. Our study objective was to characterize the knowledge, attitudes, and beliefs of primary care providers about implementing LDCT screening. Methods We conducted semistructured interviews with primary care providers practicing in New Mexico clinics for underserved minority populations. The interviews, conducted from February through September 2014, focused on providers’ tobacco cessation efforts, lung cancer screening practices, perceptions of NLST and screening guidelines, and attitudes about informed decision making for cancer screening. Investigators iteratively reviewed transcripts to create a coding structure. Results We reached thematic saturation after interviewing 10 providers practicing in 6 urban and 4 rural settings; 8 practiced at federally qualified health centers. All 10 providers promoted smoking cessation, some screened with chest x-rays, and none screened with LDCT. Not all were aware of NLST results or current guideline recommendations. Providers viewed study results skeptically, particularly the 95% false-positive rate, the need to screen 320 patients to prevent 1 lung cancer death, and the small proportion of minority participants. Providers were uncertain whether New Mexico had the necessary infrastructure to support high-quality screening, and worried about access barriers and financial burdens for rural, underinsured populations. Providers noted the complexity of discussing benefits and harms of screening and surveillance with their patient population. Conclusion Providers have several concerns about the feasibility and appropriateness of implementing LDCT screening. Effective lung cancer screening programs will need to educate providers and patients to support informed decision making and to ensure that high-quality screening can be efficiently delivered in community practice. PMID:26160294

High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

PubMed

Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Induction and repair of HZE induced cytogenetic damage

NASA Technical Reports Server (NTRS)

Brooks, A. L.; Bao, S.; Rithidech, K.; Chrisler, W. B.; Couch, L. A.; Braby, L. A.

2001-01-01

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

Dosimetric impact of different CT datasets for stereotactic treatment planning using 3D conformal radiotherapy or volumetric modulated arc therapy.

PubMed

Oechsner, Markus; Odersky, Leonhard; Berndt, Johannes; Combs, Stephanie Elisabeth; Wilkens, Jan Jakob; Duma, Marciana Nona

2015-12-01

The purpose of this study was to assess the impact on dose to the planning target volume (PTV) and organs at risk (OAR) by using four differently generated CT datasets for dose calculation in stereotactic body radiotherapy (SBRT) of lung and liver tumors. Additionally, dose differences between 3D conformal radiotherapy and volumetric modulated arc therapy (VMAT) plans calculated on these CT datasets were determined. Twenty SBRT patients, ten lung cases and ten liver cases, were retrospectively selected for this study. Treatment plans were optimized on average intensity projection (AIP) CTs using 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT). Afterwards, the plans were copied to the planning CTs (PCT), maximum intensity projection (MIP) and mid-ventilation (MidV) CT datasets and dose was recalculated keeping all beam parameters and monitor units unchanged. Ipsilateral lung and liver volumes and dosimetric parameters for PTV (Dmean, D2, D98, D95), ipsilateral lung and liver (Dmean, V30, V20, V10) were determined and statistically analysed using Wilcoxon test. Significant but small mean differences were found for PTV dose between the CTs (lung SBRT: ≤2.5 %; liver SBRT: ≤1.6 %). MIPs achieved the smallest lung and the largest liver volumes. OAR mean doses in MIP plans were distinctly smaller than in the other CT datasets. Furthermore, overlapping of tumors with the diaphragm results in underestimated ipsilateral lung dose in MIP plans. Best agreement was found between AIP and MidV (lung SBRT). Overall, differences in liver SBRT were smaller than in lung SBRT and VMAT plans achieved slightly smaller differences than 3D-CRT plans. Only small differences were found for PTV parameters between the four CT datasets. Larger differences occurred for the doses to organs at risk (ipsilateral lung, liver) especially for MIP plans. No relevant differences were observed between 3D-CRT or VMAT plans. MIP CTs are not appropriate for OAR dose assessment. PCT, AIP and MidV resulted in similar doses. If a 4DCT is acquired PCT can be omitted using AIP or MidV for treatment planning.

Plasma Doping—Enabling Technology for High Dose Logic and Memory Applications

NASA Astrophysics Data System (ADS)

Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

2008-11-01

As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

[Study on ultra-structural pathological changes of rats poisoned by tetramine].

PubMed

Zhi, Chuan-hong; Liu, Liang; Liu, Yan

2005-05-01

To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. The toxic target organs of tetramine are the heart, brain and liver.

Radiopharmaceutical considerations for using Tc-99m MAA in lung transplant patients.

PubMed

Ponto, James A

2010-01-01

To elucidate radiopharmaceutical considerations for using technetium Tc-99m albumin aggregated (Tc-99m MAA) in lung transplant patients and to establish an appropriate routine dose and preparation procedure. Tertiary care academic hospital during May 2007 to May 2009. Nuclear pharmacist working in nuclear medicine department. Radiopharmaceutical considerations deemed important for the use of Tc-99m MAA in lung transplant patients included radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity. Evaluation of our initial 12-month experience, published literature, and professional practice guidelines provided the basis for establishing an appropriate dose and preparation procedure of Tc-99m MAA for use in lung transplant patients. Radiochemical purity at typical incubation times and image quality in subsequent lung transplant patients imaged during the next 12 months. Based on considerations of radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity, a routine dose consisting of 3 mCi (111 MBq) and 100,000 particles of Tc-99m MAA for planar perfusion lung imaging of adult lung transplant patients was established as reasonable and appropriate. MAA kits were prepared with a more reasonable amount of Tc-99m and yielded high radiochemical purity values in typical incubation times. Images have continued to be of high diagnostic quality. Tc-99m MAA used for lung transplant imaging can be readily prepared with high radiochemical purity to provide a dose of 3 mCi (111 GBq)/100,000 particles, which provides images of high diagnostic quality.

CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

PubMed Central

Greenberg, Alissa K.; Lu, Feng; Goldberg, Judith D.; Eylers, Ellen; Tsay, Jun-Chieh; Yie, Ting-An; Naidich, David; McGuinness, Georgeann; Pass, Harvey; Tchou-Wong, Kam-Meng; Addrizzo-Harris, Doreen; Chachoua, Abraham; Crawford, Bernard; Rom, William N.

2012-01-01

Background Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. Methods We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). Results The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. Conclusions NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases. PMID:22768300

K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose

EPA Science Inventory

K-Ras mutant fraction (MF) was measured to examine the default assumption of low dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of ten male A/J mice (7-9 weeks-old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P, and were sacrifi...

SU-C-BRB-02: Symmetric and Asymmetric MLC Based Lung Shielding and Dose Optimization During Translating Bed TBI

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

Ahmed, S; Kakakhel, MB; Ahmed, SBS

2015-06-15

Purpose: The primary aim was to introduce a dose optimization method for translating bed total body irradiation technique that ensures lung shielding dynamically. Symmetric and asymmetric dynamic MLC apertures were employed for this purpose. Methods: The MLC aperture sizes were defined based on the radiological depth values along the divergent ray lines passing through the individual CT slices. Based on these RD values, asymmetrically shaped MLC apertures were defined every 9 mm of the phantom in superior-inferior direction. Individual MLC files were created with MATLAB™ and were imported into Eclipse™ treatment planning system for dose calculations. Lungs can be shieldedmore » to an optimum level by reducing the MLC aperture width over the lungs. The process was repeated with symmetrically shaped apertures. Results: Dose-volume histogram (DVH) analysis shows that the asymmetric MLC based technique provides better dose coverage to the body and optimum shielding of the lungs compared to symmetrically shaped beam apertures. Midline dose homogeneity is within ±3% with asymmetric MLC apertures whereas it remains within ±4.5% with symmetric ones (except head region where it drops down to −7%). The substantial over and under dosage of ±5% at tissue interfaces has been reduced to ±2% with asymmetric MLC technique. Lungs dose can be reduced to any desired limit. In this experiment lungs dose was reduced to 80% of the prescribed dose, as was desired. Conclusion: The novel asymmetric MLC based technique assures optimum shielding of OARs (e.g. lungs) and better 3-D dose homogeneity and body-dose coverage in comparison with the symmetric MLC aperture optimization. The authors acknowledge the financial and infrastructural support provided by Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad and Aga Khan University Hospital (AKUH), Karachi during the course of this research project. Authors have no conflict of interest with any national / international body for the presented work.« less

Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light.

PubMed

Vankayala, Raviraj; Lin, Chun-Chih; Kalluru, Poliraju; Chiang, Chi-Shiun; Hwang, Kuo Chu

2014-07-01

Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses. Copyright © 2014 Elsevier Ltd. All rights reserved.

MICRO DOSE ASESSMENT OF INHALED PARTICLES IN HUMAN LUNGS: A STEP CLOSER TOWARDS THE TARGET TISSUE DOSE

EPA Science Inventory

Rationale: Inhaled particles deposit inhomogeneously in the lung and this may result in excessive deposition dose at local regions of the lung, particularly at the anatomic sites of bifurcations and junctions of the airways, which in turn leads to injuries to the tissues and adve...

Accuracy of computer-aided design models of the jaws produced using ultra-low MDCT doses and ASIR and MBIR.

PubMed

Al-Ekrish, Asma'a A; Alfadda, Sara A; Ameen, Wadea; Hörmann, Romed; Puelacher, Wolfgang; Widmann, Gerlig

2018-06-16

To compare the surface of computer-aided design (CAD) models of the maxilla produced using ultra-low MDCT doses combined with filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) reconstruction techniques with that produced from a standard dose/FBP protocol. A cadaveric completely edentulous maxilla was imaged using a standard dose protocol (CTDIvol: 29.4 mGy) and FBP, in addition to 5 low dose test protocols (LD1-5) (CTDIvol: 4.19, 2.64, 0.99, 0.53, and 0.29 mGy) reconstructed with FBP, ASIR 50, ASIR 100, and MBIR. A CAD model from each test protocol was superimposed onto the reference model using the 'Best Fit Alignment' function. Differences between the test and reference models were analyzed as maximum and mean deviations, and root-mean-square of the deviations, and color-coded models were obtained which demonstrated the location, magnitude and direction of the deviations. Based upon the magnitude, size, and distribution of areas of deviations, CAD models from the following protocols were comparable to the reference model: FBP/LD1; ASIR 50/LD1 and LD2; ASIR 100/LD1, LD2, and LD3; MBIR/LD1. The following protocols demonstrated deviations mostly between 1-2 mm or under 1 mm but over large areas, and so their effect on surgical guide accuracy is questionable: FBP/LD2; MBIR/LD2, LD3, LD4, and LD5. The following protocols demonstrated large deviations over large areas and therefore were not comparable to the reference model: FBP/LD3, LD4, and LD5; ASIR 50/LD3, LD4, and LD5; ASIR 100/LD4, and LD5. When MDCT is used for CAD models of the jaws, dose reductions of 86% may be possible with FBP, 91% with ASIR 50, and 97% with ASIR 100. Analysis of the stability and accuracy of CAD/CAM surgical guides as directly related to the jaws is needed to confirm the results.

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

PubMed

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

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

Tobler, Matt; Watson, Gordon; Leavitt, Dennis

Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We havemore » developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord.« less

Radiation Exposure of Interventional Radiologists During Computed Tomography Fluoroscopy-Guided Renal Cryoablation and Lung Radiofrequency Ablation: Direct Measurement in a Clinical Setting.

PubMed

Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Iguchi, Toshihiro; Fujiwara, Hiroyasu; Kawabata, Takahiro; Yamauchi, Takatsugu; Yamaguchi, Takuya; Kanazawa, Susumu

2016-06-01

Computed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking. Radiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator's finger skin was measured using thermoluminescent dosimeter rings. The mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator's finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA. Radiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.

Computed Tomography Screening for Lung Cancer in the National Lung Screening Trial

PubMed Central

Black, William C.

2016-01-01

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT versus chest radiography reduced lung cancer mortality by 16% to 20%. More recently, a cost-effectiveness analysis (CEA) of CT screening for lung cancer versus no screening in the NLST was performed. The CEA conformed to the reference-case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine, including the use of the societal perspective and an annual discount rate of 3%. The CEA was based on several important assumptions. In this paper, I review the methods and assumptions used to obtain the base case estimate of $81,000 per quality-adjusted life-year gained. In addition, I show how this estimate varied widely among different subsets and when some of the base case assumptions were changed and speculate on the cost-effectiveness of CT screening for lung cancer outside the NLST. PMID:25635704

Subchronic inhalation toxicity of gold nanoparticles

PubMed Central

2011-01-01

Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose-dependent accumulation of gold in only lungs and kidneys with a gender-related difference in gold nanoparticles content in kidneys. Conclusions Lungs were the only organ in which there were dose-related changes in both male and female rats. Changes observed in lung histopathology and function in high-dose animals indicate that the highest concentration (20 μg/m3) is a LOAEL and the middle concentration (0.38 μg/m3) is a NOAEL for this study. PMID:21569586

PRECLINICAL PHARMACOKINETIC ANALYSIS OF (E)-METHYL-4-ARYL-4-OXABUT-2-ENOATE, A NOVEL SER/THR PROTEIN KINASE B INIBITOR, IN RATS.

PubMed

Zhai, Qian-Qian; Pang, Jing; Li, Guo-Qing; Li, Cong-Ran; Wang, Yu-Cheng; Yu, Li-Yan; Li, Jian; YOUm, Xue-Fu

2017-01-01

(E)-Methyl-4-aryl-4-oxabut-2-enoate, designated YH-8, is a novel Serflhr protein kinase B (PknB) inhibitor, which is designed for the treatment of tuberculosis. The aim of this study was to investigate the pharmacokinetics, bioavailability, tissue distribution and excretion characteristics of YH-8 in rats and study its plasma protein binding in vitro. The pharmacokinetic properties were examined after intravenously injected YH-8 at 10 and 20 mg/kg and oral administrated YH-8 at 50, 100 and 200 mg/kg to rats. The concentrations of YH-8 in plasma were determined with LC-MS/MS, with a liquid-liquid extraction. The tissue distribution and urinary, fecal and -biliary excretion patterns of YH-8 were investigated following a single oral dosing of 100 mg/kg. The plasma protein binding rates of YH-8 were determined using ultra-filtration method. After intra- venous and oral administration, YH-8 showed dose-independent pharmacokinetic characteristics, with T(1/2) of approximately 5.5 h and 7.1 h, respectively. The oral absolute bioavailability of YH-8 was relatively low (about 12%). YH-8 was widely distributed in various tissues and showed substantial deposition in intestine, stomach, liver, lung and kidney. The drug was mainly eliminated via fecal excretion and its binding rate with plasma protein was concentration-dependent. In conclusion, this study as first provided the full pharmacokinetic characteristics of YH-8, which would be helpful for its further development and clinical application.

From Mice and Men to Earth and Space: Joint NASA-NCI Workshop on Lung Cancer Risk Resulting from Space and Terrestrial Radiation

PubMed Central

Shay, Jerry W.; Cucinotta, Francis A.; Sulzman, Frank M.; Coleman, C. Norman; Minna, John D.

2011-01-01

On June 27–28, 2011 scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA – available data suggest lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high energy protons from solar flares and not from gamma radiation. By contrast the NCI is endeavoring to estimate the increased lung cancer risk from the potential wide-spread implementation of computed tomography (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be x-rays from CT scans from the screening (which uses “low dose” CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low dose Earth radiation exposure. The workshop examined preclinical models, epidemiology, molecular markers, “omics” technology, radiobiology issues, and lung stem cells (LSC) that relate to the development of lung cancer. PMID:21900398

Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report.

PubMed

Chinniah, Keith J; Mody, Girish M

2017-06-01

Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years later she had a myositis flare with severe dysphagia. Her myositis improved after high doses of corticosteroids, azathioprine and two doses of intravenous immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia gradually resolved and the PEG tube was removed within two months. She received another dose of rituximab six months later and continued low dose prednisone and azathioprine. Her muscle power improved, weight returned to normal and she remained well 20 months after hospital discharge. Our patient with SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and remained in remission 20 months after hospital discharge.

Mortality among mound workers exposed to polonium-210 and other sources of radiation, 1944-1979.

PubMed

Boice, John D; Cohen, Sarah S; Mumma, Michael T; Ellis, Elizabeth Dupree; Cragle, Donna L; Eckerman, Keith F; Wallace, Phillip W; Chadda, Bandana; Sonderman, Jennifer S; Wiggs, Laurie D; Richter, Bonnie S; Leggett, Richard W

2014-02-01

Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. Cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944-1972) in combination with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88-0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79-0.93), lung cancer (SMR 0.85; 95% CI 0.74-0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15-2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23-1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97-1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63-1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95-1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.

Mortality Among Mound Workers Exposed to Polonium-210 and Other Sources of Radiation, 1944–1979

DOE PAGES

Boice, John D.; Cohen, Sarah S.; Mumma, Michael T.; ...

2014-02-14

Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. In this paper, cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944–1972) in combinationmore » with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88–0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79–0.93), lung cancer (SMR 0.85; 95% CI 0.74–0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15–2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23–1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97–1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63–1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95–1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Finally, larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.« less

Mortality Among Mound Workers Exposed to Polonium-210 and Other Sources of Radiation, 1944–1979

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

Boice, John D.; Cohen, Sarah S.; Mumma, Michael T.

Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. In this paper, cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944–1972) in combinationmore » with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88–0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79–0.93), lung cancer (SMR 0.85; 95% CI 0.74–0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15–2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23–1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97–1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63–1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95–1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Finally, larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.« less

Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer.

PubMed

Schild, Steven E; Fan, Wen; Stinchcombe, Thomas E; Vokes, Everett E; Ramalingam, Suresh S; Bradley, Jeffrey D; Kelly, Karen; Pang, Herbert H; Wang, Xiaofei

2018-04-21

Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED). Hazard ratios(HRs) for overall survival were calculated with univariable and multivariable Cox models. TRT doses ranged from 60 to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT(univariable HR,1.37;95%CI,1.24-1.51,p<0.0001;multivariable HR,1.31;95%CI,1.08-1.59,p=0.002). The median survival of the IF and ENI patients were 24 and 16 months, respectively. Patients were divided into 3 dose groups: low total dose(60 Gy), medium total dose(>60Gy-66Gy) and high total dose(>66Gy-74 Gy). With reference to the low dose group, the multivariable HR's were 1.08 for the medium dose group(95%CI=0.93-1.25) and 1.12 for the high dose group(CI=0.97-1.30).The univariate p=0.054 and multivariable p=0.17. BED was grouped as follows: low(<55.5Gy 10 ), medium(=55.5 Gy 10) , or high(>55.5 Gy 10 ). With reference to the low BED group, the HR was 1.00(95%CI=0.85-1.18) for the medium BED group and 1.10(95%CI=0.93-1.31) for the high BED group. The univariable p=0.076 and multivariable p=0.16. For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT. Copyright © 2018. Published by Elsevier Inc.

The Role of Alveolar Epithelium in Radiation-Induced Lung Injury

PubMed Central

Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

2013-01-01

Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11–13 Gy) and fractionated doses (24–36 Gy) of 137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis. PMID:23326473

Density overwrites of internal tumor volumes in intensity modulated proton therapy plans for mobile lung tumors

NASA Astrophysics Data System (ADS)

Botas, Pablo; Grassberger, Clemens; Sharp, Gregory; Paganetti, Harald

2018-02-01

The purpose of this study was to investigate internal tumor volume density overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan degradation of mobile lung tumors. Four planning paradigms were compared for nine lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical target volume (ICTV) structures were defined encompassing their respective volumes in every 4DCT phase. The paradigms use different planning CT (pCT) created from the average intensity projection (AIP) of the 4DCT, overwriting the density within the IGTV to account for movement. The density overwrites were: (a) constant filling with 100 HU (C100) or (b) 50 HU (C50), (c) maximum intensity projection (MIP) across phases, and (d) water equivalent path length (WEPL) consideration from beam’s-eye-view. Plans were created optimizing dose-influence matrices calculated with fast GPU Monte Carlo (MC) simulations in each pCT. Plans were evaluated with MC on the 4DCTs using a model of the beam delivery time structure. Dose accumulation was performed using deformable image registration. Interplay effect was addressed applying 10 times rescanning. Significantly less DVH metrics degradation occurred when using MIP and WEPL approaches. Target coverage (D99≥slant 70 Gy(RBE)) was fulfilled in most cases with MIP and WEPL (D{{99}WEPL}=69.2+/- 4.0 Gy (RBE)), keeping dose heterogeneity low (D5-D{{95}WEPL}=3.9+/- 2.0 Gy(RBE)). The mean lung dose was kept lowest by the WEPL strategy, as well as the maximum dose to organs at risk (OARs). The impact on dose levels in the heart, spinal cord and esophagus were patient specific. Overall, the WEPL strategy gives the best performance and should be preferred when using a 3D static geometry for lung cancer IMPT treatment planning. Newly available fast MC methods make it possible to handle long simulations based on 4D data sets to perform studies with high accuracy and efficiency, even prior to individual treatment planning.

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

Clinical Value of a One-Stop-Shop Low-Dose Lung Screening Combined with (18)F-FDG PET/CT for the Detection of Metastatic Lung Nodules from Colorectal Cancer.

PubMed

Han, Yeon-Hee; Lim, Seok Tae; Jeong, Hwan-Jeong; Sohn, Myung-Hee

2016-06-01

The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with (18)F-fluoro-2-deoxyglucose positron emission tomography with CT ((18)F-FDG PET/CT) compared with conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with (18)F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of (18)F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of (18)F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of (18)F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional lung setting image and additional LD-HRCT were 0.712 and 0.827 respectively. Additional LD-HRCT with maximum inspiration was superior to conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer (P < 0.05).

Ionizing radiation: future etiologic research and preventive strategies.

PubMed

Darby, S C; Inskip, P D

1995-11-01

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies.

Ionizing radiation: future etiologic research and preventive strategies.

PubMed Central

Darby, S C; Inskip, P D

1995-01-01

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies. PMID:8741792

Ghrelin-Induced Orexigenic Effect in Rats Depends on the Metabolic Status and Is Counteracted by Peripheral CB1 Receptor Antagonism

PubMed Central

Alen, Francisco; Crespo, Inmaculada; Ramírez-López, María Teresa; Jagerovic, Nadine; Goya, Pilar; de Fonseca, Fernando Rodríguez; de Heras, Raquel Gómez; Orio, Laura

2013-01-01

Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions. PMID:23565287

Whole-body ultra-low dose CT using spectral shaping for detection of osteolytic lesion in multiple myeloma.

PubMed

Suntharalingam, Saravanabavaan; Mikat, Christian; Wetter, Axel; Guberina, Nika; Salem, Ahmed; Heil, Philipp; Forsting, Michael; Nassenstein, Kai

2018-06-01

The aim of this study was to investigate the radiation dose and image quality of a whole-body low-dose CT (WBLDCT) using spectral shaping at 100 kV (Sn 100 kV) for the assessment of osteolytic lesions in patients with multiple myeloma. Thirty consecutive patients were retrospectively selected, who underwent a WBLDCT on a third-generation dual-source CT (DSCT) (Sn 100 kV, ref. mAs: 130). They were matched with patients, who were examined on a second-generation DSCT with a standard low-dose protocol (100 kV, ref. mAs: 111). Objective and subjective image quality, radiation exposure as well as the frequency of osteolytic lesions were evaluated. All scans were of diagnostic image quality. Subjective overall image quality was significantly higher in the study group (p = 0.0003). Objective image analysis revealed that signal intensities, signal-to-noise ratio and contrast-to-noise ratio of the bony structures were equal or significantly higher in the control group. There was no significant difference in the frequency of osteolytic lesions (p = 0.259). The median effective dose of the study protocol was significantly lower (1.45 mSv vs. 5.65 mSv; p < 0.0001). WBLDCT with Sn 100 kV can obtain sufficient image quality for the depiction of osteolytic lesions while reducing the radiation dose by approximately 74%. • Spectral shaping using tin filtration is beneficial for whole-body low-dose CT • Sn 100 kV yields sufficient image quality for depiction of osteolytic lesions • Whole-body low-dose CT can be performed with a median dose of 1.5 mSv.

Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat.

PubMed

Yao, Rong; Cao, Yu; He, Ya-rong; Lau, Wayne Bond; Zeng, Zhi; Liang, Zong-an

2015-01-01

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p<0.05). Pretreatment with APN significantly attenuated the reduced cell viability and up-regulated collagen type III expression induced by PQ in lung fibroblasts, (p<0.05). APN pretreatment up-regulated AdipoR1, but not AdipoR2, expression in WI-38 fibroblasts. AdipoR1 siRNA abrogated APN-mediated protective effects in PQ-exposed fibroblasts. Taken together, our data suggests APN protects against PQ-induced pulmonary fibrosis in a dose-dependent manner, via suppression of lung fibroblast activation. Functional AdipoR1 are expressed by human WI-38 lung fibroblasts, suggesting potential future clinical applicability of APN against pulmonary fibrosis.

Low dose CT reconstruction via L1 norm dictionary learning using alternating minimization algorithm and balancing principle.

PubMed

Wu, Junfeng; Dai, Fang; Hu, Gang; Mou, Xuanqin

2018-04-18

Excessive radiation exposure in computed tomography (CT) scans increases the chance of developing cancer and has become a major clinical concern. Recently, statistical iterative reconstruction (SIR) with l0-norm dictionary learning regularization has been developed to reconstruct CT images from the low dose and few-view dataset in order to reduce radiation dose. Nonetheless, the sparse regularization term adopted in this approach is l0-norm, which cannot guarantee the global convergence of the proposed algorithm. To address this problem, in this study we introduced the l1-norm dictionary learning penalty into SIR framework for low dose CT image reconstruction, and developed an alternating minimization algorithm to minimize the associated objective function, which transforms CT image reconstruction problem into a sparse coding subproblem and an image updating subproblem. During the image updating process, an efficient model function approach based on balancing principle is applied to choose the regularization parameters. The proposed alternating minimization algorithm was evaluated first using real projection data of a sheep lung CT perfusion and then using numerical simulation based on sheep lung CT image and chest image. Both visual assessment and quantitative comparison using terms of root mean square error (RMSE) and structural similarity (SSIM) index demonstrated that the new image reconstruction algorithm yielded similar performance with l0-norm dictionary learning penalty and outperformed the conventional filtered backprojection (FBP) and total variation (TV) minimization algorithms.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

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

Rubinstein, A; Tailor, R; Melancon, A

Purpose: To simulate and measure magnetic-field-induced radiation dose effects in a mouse lung phantom. This data will be used to support pre-clinical experiments related to MRI-guided radiation therapy systems. Methods: A mouse lung phantom was constructed out of 1.5×1.5×2.0-cm{sup 3} lung-equivalent material (0.3 g/cm{sup 3}) surrounded by a 0.6-cm solid water shell. EBT3 film was inserted into the phantom and the phantom was placed between the poles of an H-frame electromagnet. The phantom was irradiated with a cobalt-60 beam (1.25 MeV) with the electromagnet set to various magnetic field strengths (0T, 0.35T, 0.9T, and 1.5T). These magnetic field strengths correspondmore » to the range of field strengths seen in MRI-guided radiation therapy systems. Dose increases at the solid-water-to-lung-interface and dose decreases at the lung-to-solid-water interface were compared with results of Monte Carlo simulations performed with MCNP6. Results: The measured dose to lung at the solid-water-to-lung interface increased by 0%, 16%, and 29% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. The dose to lung at the lung-to-solid-water interface decreased by 4%, 18%, and 24% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. Monte Carlo simulations showed dose increases of 0%, 16%, and 31% and dose decreases of 4%, 16%, and 25%. Conclusion: Only small dose perturbations were observed at the lung-solid-water interfaces for the 0.35T case, while more substantial dose perturbations were observed for the 0.9T and 1.5T cases. There is good agreement between the Monte Carlo calculations and the experimental measurements (within 2%). These measurements will aid in designing pre-clinical studies which investigate the potential biological effects of radiation therapy in the presence of a strong magnetic field. This work was partially funded by Elekta.« less

Clinical Outcomes of 130 Patients with Primary and Secondary Lung Tumors treated with Cyberknife Robotic Stereotactic Body Radiotherapy

PubMed Central

Jansen, Nicolas; Baart, Veronique; Devillers, Magali; Dechambre, David; Lenaerts, Eric; Seidel, Laurence; Barthelemy, Nicole; Berkovic, Patrick; Gulyban, Akos; Lakosi, Ferenc; Horvath, Zsolt; Coucke, Philippe A.

2017-01-01

Abstract Background Authors report clinical outcomes of patients treated with robotic stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung lesions. Patients and methods 130 patients with 160 lesions were treated with Cyberknife SBRT, including T1-3 primary lung cancers (54%), recurrent tumors (22%) and pulmonary metastases (24%). The mean biologically equivalent dose (BED10Gy) was 151 Gy (72–180 Gy). Median prescribed dose for peripheral and central lesions was 3×20 Gy and 3×15 Gy, respectively. Local control (LC), overall survival (OS), and cause-specific survival (CSS) rates, early and late toxicities are reported. Statistical analysis was performed to identify factors influencing local tumor control. Results Median follow-up time was 21 months. In univariate analysis, higher dose was associated with better LC and a cut-off value was detected at BED10Gy ≤ 112.5 Gy, resulting in 1-, 2-, and 3-year actuarial LC rates of 93%, vs 73%, 80% vs 61%, and 63% vs 54%, for the high and low dose groups, respectively (p = 0.0061, HR = 0.384). In multivariate analysis, metastatic origin, histological confirmation and larger Planning Target Volume (PTV) were associated with higher risk of local failure. Actuarial OS and CSS rates at 1, 2, and 3 years were 85%, 74% and 62%, and 93%, 89% and 80%, respectively. Acute and late toxicities ≥ Gr 3 were observed in 3 (2%) and 6 patients (5%), respectively. Conclusions Our favorable LC and survival rates after robotic SBRT, with low rates of severe toxicities, are coherent with the literature data in this mixed, non-selected study population. PMID:28740453

Pharmacokinetics of low-dose nedaplatin and validation of AUC prediction in patients with non-small-cell lung carcinoma.

PubMed

Niioka, Takenori; Uno, Tsukasa; Yasui-Furukori, Norio; Takahata, Takenori; Shimizu, Mikiko; Sugawara, Kazunobu; Tateishi, Tomonori

2007-04-01

The aim of this study was to determine the pharmacokinetics of low-dose nedaplatin combined with paclitaxel and radiation therapy in patients having non-small-cell lung carcinoma and establish the optimal dosage regimen for low-dose nedaplatin. We also evaluated predictive accuracy of reported formulas to estimate the area under the plasma concentration-time curve (AUC) of low-dose nedaplatin. A total of 19 patients were administered a constant intravenous infusion of 20 mg/m(2) body surface area (BSA) nedaplatin for an hour, and blood samples were collected at 1, 2, 3, 4, 6, 8, and 19 h after the administration. Plasma concentrations of unbound platinum were measured, and the actual value of platinum AUC (actual AUC) was calculated based on these data. The predicted value of platinum AUC (predicted AUC) was determined by three predictive methods reported in previous studies, consisting of Bayesian method, limited sampling strategies with plasma concentration at a single time point, and simple formula method (SFM) without measured plasma concentration. Three error indices, mean prediction error (ME, measure of bias), mean absolute error (MAE, measure of accuracy), and root mean squared prediction error (RMSE, measure of precision), were obtained from the difference between the actual and the predicted AUC, to compare the accuracy between the three predictive methods. The AUC showed more than threefold inter-patient variation, and there was a favorable correlation between nedaplatin clearance and creatinine clearance (Ccr) (r = 0.832, P < 0.01). In three error indices, MAE and RMSE showed significant difference between the three AUC predictive methods, and the method of SFM had the most favorable results, in which %ME, %MAE, and %RMSE were 5.5, 10.7, and 15.4, respectively. The dosage regimen of low-dose nedaplatin should be established based on Ccr rather than on BSA. Since prediction accuracy of SFM, which did not require measured plasma concentration, was most favorable among the three methods evaluated in this study, SFM could be the most practical method to predict AUC of low-dose nedaplatin in a clinical situation judging from its high accuracy in predicting AUC without measured plasma concentration.

Next-generation technologies for spatial proteomics: Integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis.

PubMed

Spraggins, Jeffrey M; Rizzo, David G; Moore, Jessica L; Noto, Michael J; Skaar, Eric P; Caprioli, Richard M

2016-06-01

MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (<5 ppm) and resolving power (∼75 000 at m/z 5000) for proteins up to ∼20 kDa. Analysis of clear cell renal cell carcinoma using MALDI FTICR IMS identified specific proteins localized to healthy tissue regions, within the tumor, and also in areas of increased vascularization around the tumor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

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

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.« less

SU-C-12A-05: Radiation Dose in High-Pitch Pediatric Cardiac CTA: Correlation Between Lung Dose and CTDIvol, DLP, and Size Specific Dose Estimates (SSDE)

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

Wang, J; Kino, A; Newman, B

2014-06-01

Purpose: To investigate the radiation dose for pediatric high pitch cardiac CTA Methods: A total of 14 cases were included in this study, with mean age of 6.2 years (ranges from 2 months to 15 years). Cardiac CTA was performed using a dual-source CT system (Definition Flash, Siemens). Tube voltage (70, 80 and 100kV) was chosen based on patient weight. All patients were scanned using a high-pitch spiral mode (pitch ranges from 2.5 to 3) with tube current modulation technique (CareDose4D, Siemens). For each case, the three dimensional dose distributions were calculated using a Monte Carlo software package (IMPACT-MC, CTmore » Image GmbH). Scanning parameters of each exam, including tube voltage, tube current, beamshaping filters, beam collimation, were defined in the Monte Carlo calculation. Tube current profile along projection angles was obtained from projection data of each tube, which included data within the over-scanning range along z direction. The volume of lungs was segmented out with CT images (3DSlicer). Lung doses of all patients were calculated and compared with CTDIvol, DLP, and SSDE. Results: The average (range) of CTDIvol, DLP and SSDE of all patients was 1.19 mGy (0.58 to 3.12mGy), 31.54 mGy*cm (12.56 to 99 mGy*cm), 2.26 mGy (1.19 to 6.24 mGy), respectively. Radiation dose to the lungs ranged from 0.83 to 4.18 mGy. Lung doses correlated with CTDIvol, DLP and SSDE with correlation coefficients(k) at 0.98, 0.93, and 0.99. However, for the cases with CTDIvol less than 1mGy, only SSDE preserved a strong correlation with lung doses (k=0.83), while much weaker correlations were found for CTDIvol (k=0.29) and DLP (k=-0.47). Conclusion: Lung doses to pediatric patients during Cardiac CTA were estimated. SSDE showed the most robust correlation with lung doses in contrast to CTDIvol and DLP.« less

Lung Dosimetry for Radioiodine Treatment Planning in the Case of Diffuse Lung Metastases

PubMed Central

Song, Hong; He, Bin; Prideaux, Andrew; Du, Yong; Frey, Eric; Kasecamp, Wayne; Ladenson, Paul W.; Wahl, Richard L.; Sgouros, George

2010-01-01

The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua– Leeper method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging–based absorbed dose calculation for tumor and normal lungs. Methods A pediatric thyroid cancer patient with diffuse lung metastases was administered 37MBq of 131I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time–activity curve for 131I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua–Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h. Results Using the MCNP4b code, both the spatial dose distribution and a dose–volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua–Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions. Conclusion MCNP4b–based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs. PMID:17138741

Poster - Thurs Eve-23: Effect of lung density and geometry variation on inhomogeneity correction algorithms: A Monte Carlo dosimetry evaluation.

PubMed

Chow, J; Leung, M; Van Dyk, J

2008-07-01

This study provides new information on the evaluation of the lung dose calculation algorithms as a function of the relative electron density of lung, ρ e,lung . Doses calculated using the collapsed cone convolution (CCC) and adaptive convolution (AC) algorithm in lung with the Pinnacle 3 system were compared to those calculated using the Monte Carlo (MC) simulation (EGSnrc-based code). Three groups of lung phantoms, namely, "Slab", "Column" and "Cube" with different ρ e,lung (0.05-0.7), positions, volumes and shapes of lung in water were used. 6 and 18MV photon beams with 4×4 and 10×10cm 2 field sizes produced by a Varian 21EX Linac were used in the MC dose calculations. Results show that the CCC algorithm agrees well with AC to within ±1% for doses calculated in the lung phantoms, indicating that the AC, with 3-4 times less computing time required than CCC, is a good substitute for the CCC method. Comparing the CCC and AC with MC, dose deviations are found when ρ e,lung are ⩽0.1-0.3. The degree of deviation depends on the photon beam energy and field size, and is relatively large when high-energy photon beams with small field are used. For the penumbra widths (20%-80%), the CCC and AC agree well with MC for the "Slab" and "Cube" phantoms with the lung volumes at the central beam axis (CAX). However, deviations >2mm occur in the "Column" phantoms, with two lung volumes separated by a water column along the CAX, using the 18MV (4×4cm 2 ) photon beams with ρ e,lung ⩽0.1. © 2008 American Association of Physicists in Medicine.

A biomechanical hypothesis for the pathophysiology of apical lung disease.

PubMed

Casha, Aaron R; Manché, Alexander; Camilleri, Liberato; Gatt, Ruben; Dudek, Krzysztof; Pace-Bardon, Michael; Gauci, Marilyn; Grima, Joseph N

2016-07-01

A hypothesis is presented suggesting that the pathogenesis of apical lung disease is due to progression of subclinical congenital apical bullae in people with low Body Mass Index (BMI), a combination present in 15% of the population, due to high pleural stress levels present in the antero-posteriorly flattened chests of these individuals. The hypothesis was tested for validity in two apical lung pathologies with widespread epidemiological literature, namely tuberculosis (TB) and primary spontaneous pneumothorax (PSP), assessing whether the hypothesis could identify high-risk populations, explain exceptional cases like apical lower lobe disease and confirm predictions. The biomechanical hypothesis can explain the high-risk factors of apical location, age, gender and low-BMI build, as well as the occurrence of disease in the apex of the lower lobe, in both TB and PSP patients. A predicted common pathogenesis for apical lung disease was confirmed by the higher-than-expected incidence of concomitant TB and PSP. Pleural stress levels depend on chest wall shape, but are highest in the apex of young males with low BMI, leading to growth of congenital bullae that can eventually limit clearance inhaled material, superinfect or burst. This hypothesis suggests that low-dose computerized tomography may be used to screen for TB eradication. This paper is the first to propose a biomechanical mechanism for all apical lung disease pathophysiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-E-T-632: A Dosimetric Comparison of the 3D-CRT Planning of Chest Wall in Post-Mastectomy Breast Cancer Patients, with and Without Breast Board Setup

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

Muzaffar, Ambreen; Masood, Asif; Ullah, Haseeb

2014-06-15

Purpose: Breast boards are used in breast radiation which increases normal lung and heart doses, when supraclavicular field is included. Therefore, in this study through dose volume histogram (DVHs), lung and heart doses comparison was done between two different setups i.e. with and without breast board, for the treatment of left chest wall and supraclavicular fossa in postmastectomy left breast cancer. Methods: In this study, CT-Simulation scans of ten breast cancer patients were done with and without breast board, at Shifa International Hospitals Islamabad, to investigate the differences between the two different setups of the irradiation of left chest wallmore » in terms of lung and heart doses. For immobilization, support under the neck, shoulders and arms was used. Precise PLAN 2.15 treatment planning system (TPS) was used for 3D-CRT planning. The total prescribed dose for both the plans was 5000 cGy/25 fractions. The chest wall was treated with a pair of tangential photon fields and the upper supraclavicular nodal regions were treated with an anterior photon field. A mono-isocentric technique was used to match the tangential fields with the anterior field at the isocentre. The dose volume histogram was used to compare the doses of heart and ipsilateral lung. Results: Both the plans of each patient were generated and compared. DVH results showed that for the same PTV dose coverage, plans without breast board resulted in a reduction of lung and heart doses compared with the plans with breast board. There was significant reductions in V20, V<25 and mean doses for lung and V<9 and mean doses for heart. Conclusion: In comparison of both the plans, setup without breast board significantly reduced the dose-volume of the ipsilateral lung and heart in left chest wall patients. Waived registration request has been submitted.« less

WE-B-207-00: CT Lung Cancer Screening Part 1

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

NONE

2015-06-15

The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Undermore » the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan parameters. This session will review the results and summarize the individualized doses to major organs and the mean effective dose and CTDIvol estimate for 66,157 PA chest and 23,773 CT examinations respectively, using size-dependent computational phantoms coupled with Monte Carlo calculations. Learning Objectives: Review and summarize relevant NLST findings and conclusions. Understand the scope and scale of the NLST specific to participant dosimetry. Provide a comprehensive review of NLST participant dosimetry assessments. Summarize the results of an investigation providing individualized organ dose estimates for NLST participant cohorts.« less

Dosimetric study of a brachytherapy treatment of esophagus with Brazilian 192Ir sources using an anthropomorphic phantom

NASA Astrophysics Data System (ADS)

Neves, Lucio P.; Santos, William S.; Gorski, Ronan; Perini, Ana P.; Maia, Ana F.; Caldas, Linda V. E.; Orengo, Gilberto

2014-11-01

Several radioisotopes are produced at Instituto de Pesquisas Energéticas e Nucleares for the use in medical treatments, including the activation of 192Ir sources. These sources are suitable for brachytherapy treatments, due to their low or high activity, depending on the concentration of 192Ir, easiness to manufacture, small size, stable daughter products and the possibility of re-utilization. They may be used for the treatment of prostate, cervix, head and neck, skin, breast, gallbladder, uterus, vagina, lung, rectum, and eye cancer treatment. In this work, the use of some 192Ir sources was studied for the treatment of esophagus cancer, especially the dose determination of important structures, such as those on the mediastinum. This was carried out utilizing a FASH anthropomorphic phantom and the MCNP5 Monte Carlo code to transport the radiation through matter. It was possible to observe that the doses at lungs, breast, esophagus, thyroid and heart were the highest, which was expected due to their proximity to the source. Therefore, the data are useful to assess the representative dose specific to brachytherapy treatments on the esophagus for radiation protection purposes. The use of brachytherapy sources was studied for the treatment of esophagus cancer. FASH anthropomorphic phantom and MCNP5 Monte Carlo code were employed. The doses at lungs, breast, esophagus, thyroid and heart were the highest. The data is useful to assess the representative doses of treatments on the esophagus.

Update on Postnatal Steroids.

PubMed

Halliday, Henry L

2017-01-01

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention. © 2017 S. Karger AG, Basel.

Environmental radiation and the lung

PubMed Central

Hamrick, Philip E.; Walsh, Phillip J.

1974-01-01

Environmental sources of radioactive materials and their relation to lung doses and lung burdens are described. The approaches used and the problems encountered in estimating lung doses are illustrated. Exposure to radon daughter products is contrasted to exposure to plutonium as particular examples of the hazards associated with radioactive materials of different chemical and physical characteristics. PMID:4620334

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.

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy.

PubMed

Sutherland, J G H; Miksys, N; Furutani, K M; Thomson, R M

2014-01-01

To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for (125)I, (103)Pd, and (131)Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue assignment within lung contours are employed in generated phantoms, this erroneous assignment is reduced, generally resulting in higher doses. Lung-constrained tissue assignment also results in increased doses in regions of interest due to a reduction in the erroneous assignment of adipose to voxels within lung contours. Differences in dose metrics calculated for different computational phantoms are sensitive to radionuclide photon spectra with the largest differences for (103)Pd seeds and smallest but still considerable differences for (131)Cs seeds. Despite producing differences in CT images, dose metrics calculated using the STR, fan beam + STR, and 3D median filter techniques produce similar dose metrics. Results suggest that the accuracy of dose distributions for permanent implant lung brachytherapy is improved by applying lung-constrained tissue assignment schemes to metallic artifact corrected images.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy.

PubMed

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-11-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929-1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

PubMed Central

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-01-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy. PMID:22915782

SU-E-T-335: Dosimetric Investigation of An Advanced Rotating Gamma Ray System for Imaged Guided Radiation Therapy

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

Ma, C; Eldib, A; Chibani, O

2015-06-15

Purpose: Co-60 beams have unique dosimetric properties for cranial treatments and thoracic cancers. The conventional concern about the high surface dose is overcome by modern system designs with rotational treatment techniques. This work investigates a novel rotational Gamma ray system for image-guided, external beam radiotherapy. Methods: The CybeRT system (Cyber Medical Corp., China) consists of a ring gantry with either one or two treatment heads containing a Gamma source and a multileaf collimator (MLC). The MLC has 60 paired leaves, and the maximum field size is either 40cmx40cm (40 pairs of 0.5cm central leaves, 20 pairs of 1cm outer leaves),more » or 22cmx40cm (32 pairs of 0.25cm central leaves, 28 pairs of 0.5cm outer leaves). The treatment head(s) can swing 35° superiorly and 8° inferiorly, allowing a total of 43° non-coplanar beam incident. The treatment couch provides 6-degrees-of-freedom motion compensation and the kV cone-beam CT system has a spatial resolution of 0.4mm. Monte Carlo simulations were used to compute dose distributions and compare with measurements. A retrospective study of 98 previously treated patients was performed to compare CybeRT with existing RT systems. Results: Monte Carlo results confirmed the CybeRT design parameters including output factors and 3D dose distributions. Its beam penumbra/dose gradient was similar to or better than that of 6MV photon beams and its isocenter accuracy is 0.3mm. Co-60 beams produce lower-energy secondary electrons that exhibit better dose properties in low-density lung tissues. Because of their rapid depth dose falloff, Co-60 beams are favorable for peripheral lung tumors with half-arc arrangements to spare the opposite lung and critical structures. Superior dose distributions were obtained for head and neck, breast, spine and lung tumors. Conclusion: Because of its accurate dose delivery and unique dosimetric properties of C-60 sources, CybeRT is ideally suited for advanced SBRT as well as conventional RT. This work was partially supported by Cyber Medical Corp.« less

Feasibility of ultra low-dose thallium stress-redistribution protocol including prone imaging in obese patients using CZT camera.

PubMed

Kincl, Vladimír; Kamínek, Milan; Vašina, Jiří; Panovský, Roman; Havel, Martin

2016-09-01

High efficiency cadmium-zinc-telluride (CZT) cameras provide an opportunity to lower the injected activities of radiopharmaceuticals for single photon emission tomography (SPECT) myocardial perfusion imaging (MPI). The limits for reducing activities of thallium have not been determined, particularly in obese patients. After an injection of 0.7 megabecquerel (MBq) of thallium/kg, we collected an average 1.5 million counts for the 10-min acquisition in a pilot cohort of ten patients. After extrapolation, we reduced the administered activity to 0.5 MBq/kg to obtain the expected 1 million counts. We studied the image quality in 124 patients (86 men, 43 obese with body mass index over 30 kg/m 2 ) referred for MPI. The quality of images was assessed by a number of recorded counts and visually by a four-grade scale (one-poor quality, four-excellent quality). In non-obese and obese patients, the average number of recorded counts was 1.1 vs. 1.07 million counts for the 10-min stress acquisition, 1.04 vs. 1.06 million counts for the 13-min rest acquisition, and the average quality score was 3.97 vs. 3.90, respectively (p = NS).The mean administered activity was 39.2 ± 7 MBq for non-obese and 48.7 ± 6 for obese patients (p < 0.0001), and the calculated effective dose was 4.0 ± 0.7 and 4.9 ± 0.6 mSv respectively (p < 0.0001). The ultra-low-dose thallium stress-redistribution protocol, including post-stress prone imaging, provides good quality of images with a low radiation burden, even in obese patients.

Delivery of propellant soluble drug from a metered dose inhaler.

PubMed Central

Ashworth, H L; Wilson, C G; Sims, E E; Wotton, P K; Hardy, J G

1991-01-01

The deposition of particulate suspensions delivered from a metered dose inhaler has been investigated extensively. The distribution of propellant, delivered from a metered dose inhaler, was studied by radiolabelling it with technetium-99m hexamethylpropyleneamine oxime. Andersen sampler measurements indicated that half of the dose was associated with particles in the size range 0.5-5 microns diameter. The preparation was administered to healthy subjects by inhalation and deposition was monitored with a gamma camera. Each lung image was divided into an inner, mid, and peripheral zone. The effects on deposition of varying the size of the delivery orifice (0.46, 0.61, and 0.76 mm internal diameters) and the effect of attaching a spacer were assessed. Lung deposition was independent of the orifice size within the actuator. Without the spacer the average dose deposited in the lungs was 39%, with 15% penetrating into the peripheral part of the lungs. Attachment of the spacer to the mouth-piece increased the mean lung deposition to 57% and reduced oropharyngeal deposition. The study has shown that propellant soluble drugs can be delivered efficiently to the lungs from a metered dose inhaler. Images PMID:2038731

TH-AB-BRA-05: Lung Cannot Be Treated as Homogeneous in Radiation Transport Simulations in Magnetic Fields

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

Malkov, V; Rogers, D; Jaffray, D

2016-06-15

Purpose: Magnetic fields in MRgRT are known to induce dose perturbations near lung-tissue interfaces. The goal of this study is to determine if the heterogeneous structure of the lung influences the dose distribution in a magnetic field. Method: The dose distribution from a 4 cm X 4 cm 6 MV photon beam in a 0, 0.6, or 1.5 T magnetic field in a homogeneous lung density (0.333 g/cm{sup 3}) geometry is compared to that in a heterogeneous segmented slab configuration. The heterogeneous phantom is composed of 2/3 water vapour and 1/3 liquid water such that the overall density of themore » lung regions in the two phantoms are equivalent. The EGSnrc DOSXYZnrc user code is used with a previously implemented magnetic field transport code. Results: For water vapour gap thickness of 2 mm, compared to the homogeneous lung case (which already exhibits significant dose perturbations in a magnetic field) differences as large as 12.3 ± 0.2 % are observed for a 0.6 T field and 9.3 ± 0.1 % for a 1.5 T field at the tissuelung interface, and on the order of several percent within the lung-like tissue region for both magnetic fields. Thicker gaps produced larger deviations while a gap thickness of 0.2 mm does not result in notable differences. Regardless of gap thickness, the heterogeneities had little effect on the 0 T simulations. Further, using smaller scoring regions revealed that dose averaging effects could obscure dose differences as large as 10 – 20 % within the heterogeneous structures of the lung-like media. Conclusions: This simple model demonstrates that media heterogeneities can play an important role in MRgRT dose distributions, and care must be taken in setting up any dose calculation in the lung in the presence of a magnetic field, especially for air regions larger than 2 mm.« less

Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.

PubMed

Arya, Aditya; Sethy, Niroj Kumar; Singh, Sushil Kumar; Das, Mainak; Bhargava, Kalpana

2013-01-01

Cerium oxide nanoparticles (nanoceria) are effective at quenching reactive oxygen species (ROS) in cell culture and animal models. Although nanoceria reportedly deposit in lungs, their efficacy in conferring lung protection during oxidative stress remains unexplored. Thus, the study evaluated the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia. A total of 48 animals were randomly divided into four equal groups (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5 μg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H groups) for 5 weeks. After the final dose, H and T+H animals were challenged with hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were isolated and homogenate was obtained for analysis of ROS, lipid peroxidation, glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma was used for estimating major inflammatory cytokines using enzyme-linked immunosorbent assay. Intact lung tissues were fixed and both transmission electron microscopy and histopathological examinations were carried out separately for detecting internalization of nanoparticles as well as altered lung morphology. Spherical nanoceria of 7-10 nm diameter were synthesized using a microemulsion method, and the lung protective efficacy of the nanoceria evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria. Cumulatively, these results suggest nanoceria deposit in lungs, confer protection by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any inflammatory response.

SU-F-T-687: Comparison of SPECT/CT-Based Methodologies for Estimating Lung Dose from Y-90 Radioembolization

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

Kost, S; Yu, N; Lin, S

2016-06-15

Purpose: To compare mean lung dose (MLD) estimates from 99mTc macroaggregated albumin (MAA) SPECT/CT using two published methodologies for patients treated with {sup 90}Y radioembolization for liver cancer. Methods: MLD was estimated retrospectively using two methodologies for 40 patients from SPECT/CT images of 99mTc-MAA administered prior to radioembolization. In these two methods, lung shunt fractions (LSFs) were calculated as the ratio of scanned lung activity to the activity in the entire scan volume or to the sum of activity in the lung and liver respectively. Misregistration of liver activity into the lungs during SPECT acquisition was overcome by excluding lungmore » counts within either 2 or 1.5 cm of the diaphragm apex respectively. Patient lung density was assumed to be 0.3 g/cm{sup 3} or derived from CT densitovolumetry respectively. Results from both approaches were compared to MLD determined by planar scintigraphy (PS). The effect of patient size on the difference between MLD from PS and SPECT/CT was also investigated. Results: Lung density from CT densitovolumetry is not different from the reference density (p = 0.68). The second method resulted in lung dose of an average 1.5 times larger lung dose compared to the first method; however the difference between the means of the two estimates was not significant (p = 0.07). Lung dose from both methods were statistically different from those estimated from 2D PS (p < 0.001). There was no correlation between patient size and the difference between MLD from PS and both SPECT/CT methods (r < 0.22, p > 0.17). Conclusion: There is no statistically significant difference between MLD estimated from the two techniques. Both methods are statistically different from conventional PS, with PS overestimating dose by a factor of three or larger. The difference between lung doses estimated from 2D planar or 3D SPECT/CT is not dependent on patient size.« less

Exploring New Thermal Fog and Ultra-Low Volume Technologies to Improve Indoor Control of the Dengue Vector, Aedes aegypti (Diptera: Culicidae)

DTIC Science & Technology

2014-07-01

urban structures. An insect growth regulator was also applied to determine howwell each sprayer delivered lethal doses of active ingredient to indoor...vector suppressionwhencombinedwith aneffective insect growth regulator. However, during a dengue outbreak, either delivery system should provide an...sion(Morrisonetal. 2008,Eisenetal. 2009). Successful control programs rely on a combination of intradomi- ciliary adulticide application, larvicidal

Acute effects of pentobarbital, thiopental and urethane on lung oedema induced by alpha-naphthythiourea (ANTU).

PubMed

Sipahi, Emine; Ustün, Hüseyin; Niyazi Ayoglu, Ferruh

2002-03-01

This study was designed to investigate the possible participation of urethane, pentobarbital sodium and thiopental sodium anaesthesia in the lung oedema induced by alpha-naphthylthiourea (ANTU), which is a well known noxious chemical agent in the lung. ANTU when injected intraperitoneally (i.p.) into rats (10 mg x kg (-1) i.p.) produced lung oedema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. Administration of urethane prior to ANTU, at doses of 100 and 200mg(100g)(-1), elicited a significant and dose-dependent inhibition in LW/BW ratio and PE. Thiopental sodium at doses of 25, 50 mg x kg (-1), also produced a significant and dose-dependent inhibition of both parameters. Prior i.p. injection of pentobarbital sodium at a dose of 40 mg x kg (-1) elicited a significant inhibition in both parameters. These results suggest that i.p. urethane, thiopental sodium and pentobarbital sodium pretreatment have a prophylactic effect on ANTU-induced lung injury in rats. The possible role of the anaesthetics in lung oedema induced by ANTU and the possible underlying mechanisms are discussed. Copyright 2002 Elsevier Science Ltd.

Effects of Physalis peruviana L on Toxicity and Lung Cancer Induction by Nicotine Derived Nitrosamine Ketone in Rats.

PubMed

El-Kenawy, Ayman El-Meghawry; Elshama, Said Said; Osman, Hosam-Eldin Hussein

2015-01-01

Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability.

PubMed

van Hamersvelt, Robbert W; Willemink, Martin J; Takx, Richard A P; Eikendal, Anouk L M; Budde, Ricardo P J; Leiner, Tim; Mol, Christian P; Isgum, Ivana; de Jong, Pim A

2014-07-01

To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT). We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD). Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC. AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications. • Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

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

Arbique, G; Anderson, J; Guild, J

Purpose: The National Lung Screening Trial mandated manual low dose CT technique factors, where up to a doubling of radiation output could be used over a regular to large patient size range. Recent guidance from the AAPM and ACR for lung cancer CT screening recommends radiation output adjustment for patient size either through AEC or a manual technique chart. This study evaluated the use of AEC for output control and dose reduction. Methods: The study was performed on a multidetector helical CT scanner (Aquillion ONE, Toshiba Medical) equipped with iterative reconstruction (ADIR-3D), AEC was adjusted with a standard deviation (SD)more » image quality noise index. The protocol SD parameter was incrementally increased to reduce patient population dose while image quality was evaluated by radiologist readers scoring the clinical utility of images on a Likert scale. Results: Plots of effective dose vs. body size (water cylinder diameter reported by the scanner) demonstrate monotonic increase in patient dose with increasing patient size. At the initial SD setting of 19 the average CTDIvol for a standard size patient was ∼ 2.0 mGy (1.2 mSv effective dose). This was reduced to ∼1.0 mGy (0.5 mSv) at an SD of 25 with no noticeable reduction in clinical utility of images as demonstrated by Likert scoring. Plots of effective patient diameter and BMI vs body size indicate that these metrics could also be used for manual technique charts. Conclusion: AEC offered consistent and reliable control of radiation output in this study. Dose for a standard size patient was reduced to one-third of the 3 mGy CTDIvol limit required for ACR accreditation of lung cancer CT screening. Gary Arbique: Research Grant, Toshiba America Medical Systems; Cecelia Brewington: Research Grant, Toshiba America Medical Systems; Di Zhang: Employee, Toshiba America Medical Systems.« less

Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens

PubMed Central

2014-01-01

Background Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract. Methods Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range. Conclusions The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation. PMID:24642002

Lung Size and the Risk of Radiation Pneumonitis

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

Briere, Tina Marie, E-mail: tmbriere@mdanderson.org; Krafft, Shane; Liao, Zhongxing

2016-02-01

Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a functionmore » of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.« less

SU-E-T-639: Proton Dose Calculation for Irregular Motion Using a Sliding Interface

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

Phillips, J; Gueorguiev, G; Grassberger, C

2015-06-15

Purpose: While many techniques exist to evaluate dose to regularly moving lung targets, there are few available to calculate dose at tumor positions not present in the 4DCT. We have previously developed a method that extrapolates an existing dose to a new tumor location. In this abstract, we present a novel technique that accounts for relative anatomical shifts at the chest wall interface. We also utilize this procedure to simulate breathing motion functions on a cohort of eleven patients. Amplitudes exceeding the original range of motion were used to evaluate coverage using several aperture and smearing beam settings. Methods: Themore » water-equivalent depth (WED) technique requires an initial dose and CT image at the corresponding tumor position. Each dose volume was converted from its Cartesian geometry into a beam-specific radiological depth space. The sliding chest wall interface was determined by converting the lung contour into this same space. Any dose proximal to the initial boundary of the warped lung contour was held fixed, while the remaining distal dose was moved in the direction of motion along the interface. Results: V95 coverage was computed for each patient using the updated algorithm. Incorporation of the sliding motion yielded large dose differences, with gamma pass rates as low as 69.7% (3mm, 3%) and V95 coverage differences up to 2.0%. Clinical coverage was maintained for most patients with 5 mm excess simulated breathing motion, and up to 10 mm of excess motion was tolerated for a subset of patients and beam settings. Conclusion: We have established a method to determine the maximum allowable excess breathing motion for a given plan on a patient-by-patient basis. By integrating a sliding chest wall interface into our dose calculation technique, we have analyzed the robustness of breathing patterns that differ during treatment from at the time of 4DCT acquisition.« less

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

Kruger, R.

The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Undermore » the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan parameters. This session will review the results and summarize the individualized doses to major organs and the mean effective dose and CTDIvol estimate for 66,157 PA chest and 23,773 CT examinations respectively, using size-dependent computational phantoms coupled with Monte Carlo calculations. Learning Objectives: Review and summarize relevant NLST findings and conclusions. Understand the scope and scale of the NLST specific to participant dosimetry. Provide a comprehensive review of NLST participant dosimetry assessments. Summarize the results of an investigation providing individualized organ dose estimates for NLST participant cohorts.« less

Dosimetric effect of beam arrangement for intensity-modulated radiation therapy in the treatment of upper thoracic esophageal carcinoma.

PubMed

Fu, Yuchuan; Deng, Min; Zhou, Xiaojuan; Lin, Qiang; Du, Bin; Tian, Xue; Xu, Yong; Wang, Jin; Lu, You; Gong, Youling

2017-01-01

To evaluate the lung sparing in intensity-modulated radiation therapy (IMRT) for patients with upper thoracic esophageal tumors extending inferiorly to the thorax by different beam arrangement. Overall, 15 patient cases with cancer of upper thoracic esophagus were selected for a retrospective treatment-planning study. Intensity-modulated radiation therapy plans using 4, 5, and 7 beams (4B, 5B, and 7B) were developed for each patient by direct machine parameter optimization (DMPO). All plans were evaluated with respect to dose volumes to irradiated targets and normal structures, with statistical comparisons made between 4B with 5B and 7B intensity-modulated radiation therapy plans. Differences among plans were evaluated using a two-tailed Friedman test at a statistical significance of p < 0.05. The maximum dose, average dose, and the conformity index (CI) of planning target volume 1 (PTV1) were similar for 3 plans for each case. No significant difference of coverage for planning target volume 1 and maximum dose for spinal cords were observed among 3 plans in present study (p > 0.05). The average V 5 , V 13 , V 20 , mean lung dose, and generalized equivalent uniform dose (gEUD) for the total lung were significantly lower in 4B-plans than those data in 5B-plans and 7B-plans (p < 0.01). Although the average V 30 for the total lung were significantly higher in 4B-plans than those in 5B-plans and 7B-plans (p < 0.05). In addition, when comparing with the 4B-plans, the conformity/heterogeneity index of the 5B- and 7B-plans were significantly superior (p < 0.05). The 4B-intensity-modulated radiation therapy plan has advantage to address the specialized problem of lung sparing to low- and intermediate-dose exposure in the thorax when dealing with relative long tumors extended inferiorly to the thoracic esophagus for upper esophageal carcinoma with the cost for less conformity. Studies are needed to compare the superiority of volumetric modulated arc therapy with intensity-modulated radiation therapy technique. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Comparing Effective Doses During Image-Guided Core Needle Biopsies with Computed Tomography Versus C-Arm Cone Beam CT Using Adult and Pediatric Phantoms.

PubMed

Ben-Shlomo, A; Cohen, D; Bruckheimer, E; Bachar, G N; Konstantinovsky, R; Birk, E; Atar, E

2016-05-01

To compare the effective doses of needle biopsies based on dose measurements and simulations using adult and pediatric phantoms, between cone beam c-arm CT (CBCT) and CT. Effective doses were calculated and compared based on measurements and Monte Carlo simulations of CT- and CBCT-guided biopsy procedures of the lungs, liver, and kidney using pediatric and adult phantoms. The effective doses for pediatric and adult phantoms, using our standard protocols for upper, middle and lower lungs, liver, and kidney biopsies, were significantly lower under CBCT guidance than CT. The average effective dose for a 5-year old for these five biopsies was 0.36 ± 0.05 mSv with the standard CBCT exposure protocols and 2.13 ± 0.26 mSv with CT. The adult average effective dose for the five biopsies was 1.63 ± 0.22 mSv with the standard CBCT protocols and 8.22 ± 1.02 mSv using CT. The CT effective dose was higher than CBCT protocols for child and adult phantoms by 803 and 590% for upper lung, 639 and 525% for mid-lung, and 461 and 251% for lower lung, respectively. Similarly, the effective dose was higher by 691 and 762% for liver and 513 and 608% for kidney biopsies. Based on measurements and simulations with pediatric and adult phantoms, radiation effective doses during image-guided needle biopsies of the lung, liver, and kidney are significantly lower with CBCT than with CT.

SU-E-T-454: Dosimetric Comparison between Pencil Beam and Monte Carlo Algorithms for SBRT Lung Treatment Using IPlan V4.1 TPS and CIRS Thorax Phantom.

PubMed

Fernandez, M Castrillon; Venencia, C; Garrigó, E; Caussa, L

2012-06-01

To compare measured and calculated doses using Pencil Beam (PB) and Monte Carlo (MC) algorithm on a CIRS thorax phantom for SBRT lung treatments. A 6MV photon beam generated by a Primus linac with an Optifocus MLC (Siemens) was used. Dose calculation was done using iPlan v4.1.2 TPS (BrainLAB) by PB and MC (dose to water and dose to medium) algorithms. The commissioning of both algorithms was done reproducing experimental measurements in water. A CIRS thorax phantom was used to compare doses using a Farmer type ion chamber (PTW) and EDR2 radiographic films (KODAK). The ionization chamber, into a tissue equivalent insert, was placed in two position of lung tissue and was irradiated using three treatments plans. Axial dose distributions were measured for four treatments plans using conformal and IMRT technique. Dose distribution comparisons were done by dose profiles and gamma index (3%/3mm). For the studied beam configurations, ion chamber measurements shows that PB overestimate the dose up to 8.5%, whereas MC has a maximum variation of 1.6%. Dosimetric analysis using dose profiles shows that PB overestimates the dose in the region corresponding to the lung up to 16%. For axial dose distribution comparison the percentage of pixels with gamma index bigger than one for MC and PB was, plan 1: 95.6% versus 87.4%, plan 2: 91.2% versus 77.6%, plan 3: 99.7% versus 93.1% and for plan 4: 98.8% versus 91.7%. It was confirmed that the lower dosimetric errors calculated applying MC algorithm appears when the spatial resolution and variance decrease at the expense of increased computation time. The agreement between measured and calculated doses, in a phantom with lung heterogeneities, is better with MC algorithm. PB algorithm overestimates the doses in lung tissue, which could have a clinical impact in SBRT lung treatments. © 2012 American Association of Physicists in Medicine.

A clinical study of lung cancer dose calculation accuracy with Monte Carlo simulation.

PubMed

Zhao, Yanqun; Qi, Guohai; Yin, Gang; Wang, Xianliang; Wang, Pei; Li, Jian; Xiao, Mingyong; Li, Jie; Kang, Shengwei; Liao, Xiongfei

2014-12-16

The accuracy of dose calculation is crucial to the quality of treatment planning and, consequently, to the dose delivered to patients undergoing radiation therapy. Current general calculation algorithms such as Pencil Beam Convolution (PBC) and Collapsed Cone Convolution (CCC) have shortcomings in regard to severe inhomogeneities, particularly in those regions where charged particle equilibrium does not hold. The aim of this study was to evaluate the accuracy of the PBC and CCC algorithms in lung cancer radiotherapy using Monte Carlo (MC) technology. Four treatment plans were designed using Oncentra Masterplan TPS for each patient. Two intensity-modulated radiation therapy (IMRT) plans were developed using the PBC and CCC algorithms, and two three-dimensional conformal therapy (3DCRT) plans were developed using the PBC and CCC algorithms. The DICOM-RT files of the treatment plans were exported to the Monte Carlo system to recalculate. The dose distributions of GTV, PTV and ipsilateral lung calculated by the TPS and MC were compared. For 3DCRT and IMRT plans, the mean dose differences for GTV between the CCC and MC increased with decreasing of the GTV volume. For IMRT, the mean dose differences were found to be higher than that of 3DCRT. The CCC algorithm overestimated the GTV mean dose by approximately 3% for IMRT. For 3DCRT plans, when the volume of the GTV was greater than 100 cm(3), the mean doses calculated by CCC and MC almost have no difference. PBC shows large deviations from the MC algorithm. For the dose to the ipsilateral lung, the CCC algorithm overestimated the dose to the entire lung, and the PBC algorithm overestimated V20 but underestimated V5; the difference in V10 was not statistically significant. PBC substantially overestimates the dose to the tumour, but the CCC is similar to the MC simulation. It is recommended that the treatment plans for lung cancer be developed using an advanced dose calculation algorithm other than PBC. MC can accurately calculate the dose distribution in lung cancer and can provide a notably effective tool for benchmarking the performance of other dose calculation algorithms within patients.

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

Wang Shulian; Liao Zhongxing; Vaporciyan, Ara A.

Purpose: To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Method and Materials: Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy)more » was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V{sub dose} and absolute V{sub dose}), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS{sub dose}). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V{sub dose} or VS{sub dose}) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Results: Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving {>=}5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses {>=}5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses {>=}5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Conclusions: Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of {>=}5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.« less

Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.

PubMed

Wang, Shu-lian; Liao, Zhongxing; Vaporciyan, Ara A; Tucker, Susan L; Liu, Helen; Wei, Xiong; Swisher, Stephen; Ajani, Jaffer A; Cox, James D; Komaki, Ritsuko

2006-03-01

To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving > or = 5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses > or = 5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses > or = 5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of > or = 5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.

SU-F-T-564: 3 Year Experience of Treatment Plan QualityAssurance for Vero SBRT Patients

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

Su, Z; Li, Z; Mamalui, M

2016-06-15

Purpose: To verify treatment plan monitor units from iPlan treatment planning system for Vero Stereotactic Body Radiotherapy (SBRT) treatment using both software-based and (homogeneous and heterogeneous) phantom-based approaches. Methods: Dynamic conformal arcs (DCA) were used for SBRT treatment of oligometastasis patients using Vero linear accelerator. For each plan, Monte Carlo calculated treatment plans MU (prescribed dose to water with 1% variance) is verified first by RadCalc software with 3% difference threshold. Beyond 3% differences, treatment plans were copied onto (homogeneous) Scanditronix phantom for non-lung patients and copied onto (heterogeneous) CIRS phantom for lung patients and the corresponding plan dose wasmore » measured using a cc01 ion chamber. The difference between the planed and measured dose was recorded. For the past 3 years, we have treated 180 patients with 315 targets. Out of these patients, 99 targets treatment plan RadCalc calculation exceeded 3% threshold and phantom based measurements were performed with 26 plans using Scanditronix phantom and 73 plans using CIRS phantom. Mean and standard deviation of the dose differences were obtained and presented. Results: For all patient RadCalc calculations, the mean dose difference is 0.76% with a standard deviation of 5.97%. For non-lung patient plan Scanditronix phantom measurements, the mean dose difference is 0.54% with standard deviation of 2.53%; for lung patient plan CIRS phantom measurements, the mean dose difference is −0.04% with a standard deviation of 1.09%; The maximum dose difference is 3.47% for Scanditronix phantom measurements and 3.08% for CIRS phantom measurements. Conclusion: Limitations in secondary MU check software lead to perceived large dose discrepancies for some of the lung patient SBRT treatment plans. Homogeneous and heterogeneous phantoms were used in plan quality assurance for non-lung patients and lung patients, respectively. Phantom based QA showed the relative good agreement between iPlan calculated dose and measured dose.« less

Prediction of lung cancer incidence on the low-dose computed tomography arm of the National Lung Screening Trial: A dynamic Bayesian network

PubMed Central

Petousis, Panayiotis; Han, Simon X.; Aberle, Denise; Bui, Alex A.T.

2016-01-01

Introduction Identifying high-risk lung cancer individuals at an early disease stage is the most effective way of improving survival. The landmark National Lung Screening Trial (NLST) demonstrated the utility of low-dose computed tomography (LDCT) imaging to reduce mortality (relative to x-ray screening). As a result of the NLST and other studies, imaging-based lung cancer screening programs are now being implemented. However, LDCT interpretation results in a high number of false positives. A set of dynamic Bayesian networks (DBN) were designed and evaluated to provide insight into how longitudinal data can be used to help inform lung cancer screening decisions. Methods The LDCT arm of the NLST dataset was used to build and explore five DBNs for high-risk individuals. Three of these DBNs were built using a backward construction process, and two using structure learning methods. All models employ demographic, smoking status, cancer history, family lung cancer history, exposure risk factors, comorbidities related to lung cancer, and LDCT screening outcome information. Given the uncertainty arising from lung cancer screening, a cancer state-space model based on lung cancer staging was utilized to characterize the cancer status of an individual over time. The models were evaluated on balanced training and test sets of cancer and non-cancer cases to deal with data imbalance and overfitting. Results Results were comparable to expert decisions. The average area under the curve (AUC) of the receiver operating characteristic (ROC) for the three intervention points of the NLST trial was higher than 0.75 for all models. Evaluation of the models on the complete LDCT arm of the NLST dataset (N = 25, 486) demonstrated satisfactory generalization. Consensus of predictions over similar cases is reported in concordance statistics between the models’ and the physicians’ predictions. The models’ predictive ability with respect to missing data was also evaluated with the sample of cases that missed the second screening exam of the trial (N = 417). The DBNs outperformed comparison models such as logistic regression and naïve Bayes. Conclusion The lung cancer screening DBNs demonstrated high discrimination and predictive power with the majority of cancer and non-cancer cases. PMID:27664507

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

Patel, Pretesh R., E-mail: patel073@mc.duke.edu; Yoo, Sua; Broadwater, Gloria

Purpose: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Methods and Materials: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity wasmore » graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Results: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. Conclusions: With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.« less

Intercellular Adhesion Molecule 1 Knockout Abrogates Radiation Induced Pulmonary Inflammation

NASA Astrophysics Data System (ADS)

Hallahan, Dennis E.; Virudachalam, Subbulakshmi

1997-06-01

Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration into the irradiated lung.

Occupational radiation exposure experience: Paducah Gaseous Diffusion Plant

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

Baker, R.C.

1975-01-01

The potential for significant uranium exposure in gaseous diffusion plants is very low. The potential for significant radiation exposure in uranium hexafluoride manufacturing is very real. Exposures can be controlled to low levels only through the cooperation and commitment of facility management and operating personnel. Exposure control can be adequately monitored by a combination of air analyses, urinalyses, and measurements of internal deposition as obtained by the IVRML. A program based on control of air-borne uranium exposure has maintained the internal dose of the Paducah Gaseous Diffusion Plant workman to less than one-half the RPG dose to the lung (15more » rem/year) and probably to less than one-fourth that dose. (auth)« less

Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

PubMed

Miller, J D; Sun, M; Gilyan, A; Roy, J; Rand, T G

2010-01-05

Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (p< or =0.05; >or =1.5-fold or < or =-1.5-fold change) in the different treatment animal groups. Expression of transcriptionally regulated genes was confirmed using immunohistochemistry that demonstrated MIP-2 and Tnf-alpha staining in respiratory bronchiolar epithelia, alveolar macrophages and alveolar type II cells. The transcriptional regulation in these genes in the treatment groups suggests that they may serve central roles in the immunomodulation of toxin-induced pro-inflammatory lung responses. Hierarchical cluster analysis revealed significant patterns of gene transcription linking the response of the toxins at equimolar doses in three groups: (1) brevianamide, mycophenolic acid and neoechinulin B, (2) neoechinulin A and sterigmatocystin, and (3) cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can contribute to the development of non-allergenic respiratory health effects.

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

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

McGurk, R; Green, R; Lawrence, M

2015-06-15

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less

Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues.

PubMed

Bellavite, Paolo; Bonafini, Clara; Marzotto, Marta

Gelsemium sempervirens L. (Gelsemium) is traditionally used for its anxiolytic-like properties and its action mechanism in laboratory models are under scrutiny. Evidence from rodent models was reported suggesting the existence of a high sensitivity of central nervous system to anxiolytic power of Gelsemium extracts and Homeopathic dilutions. In vitro investigation of extremely low doses of this plant extract showed a modulation of gene expression of human neurocytes. These studies were criticized in a few commentaries, generated a debate in literature and were followed by further experimental studies from various laboratories. Toxic doses of Gelsemium cause neurological signs characterized by marked weakness and convulsions, while ultra-low doses or high Homeopathic dilutions counteract seizures induced by lithium and pilocarpine, decrease anxiety after stress and increases the anti-stress allopregnanolone hormone, through glycine receptors. Low (non-Homeopathic) doses of this plant or its alkaloids decrease neuropathic pain and c-Fos expression in mice brain and oxidative stress. Due to the complexity of the matter, several aspects deserve interpretation and the main controversial topics, with a focus on the issues of high dilution pharmacology, are discussed and clarified. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Evaluation of low-dose CT implementation for lung cancer screening in a general practice hospital

NASA Astrophysics Data System (ADS)

Karostik, D. V.; Kamyshanskaya, I. G.; Cheremisin, V. M.; Drozdov, A. A.; Vodovatov, A. V.

2018-02-01

The aim of the current study was to evaluate the possibility of the implementation of LDCT for the screening for lung cancer and tuberculosis in a typical general hospital practice. Diagnostic and economic effectiveness, patient doses and the corresponding radiation risks for LDCT were compared with the existing digital chest screening radiography. The results of the study indicate that the implementation of LDCT allowed verifying false-positive cases or providing additional excessive diagnostic information, but did not significantly improve the sensitivity of screening. Per capita costs for LDCT were higher compared to digital radiography up to a factor of 12; corresponding radiation risk - by a factor of 4. Hence, it was considered unjustified to implement LDCT in a general practice hospital.

Algorithm of pulmonary emphysema extraction using low dose thoracic 3D CT images

NASA Astrophysics Data System (ADS)

Saita, S.; Kubo, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Omatsu, H.; Tominaga, K.; Eguchi, K.; Moriyama, N.

2006-03-01

Recently, due to aging and smoking, emphysema patients are increasing. The restoration of alveolus which was destroyed by emphysema is not possible, thus early detection of emphysema is desired. We describe a quantitative algorithm for extracting emphysematous lesions and quantitatively evaluate their distribution patterns using low dose thoracic 3-D CT images. The algorithm identified lung anatomies, and extracted low attenuation area (LAA) as emphysematous lesion candidates. Applying the algorithm to 100 thoracic 3-D CT images and then by follow-up 3-D CT images, we demonstrate its potential effectiveness to assist radiologists and physicians to quantitatively evaluate the emphysematous lesions distribution and their evolution in time interval changes.

SU-D-202-01: Functional Lung Avoidance and Response-Adaptive Escalation (FLARE) RT: Feasibility of a Precision Radiation Oncology Strategy

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

Bowen, S; Lee, E; Miyaoka, R

Purpose: NSCLC patient RT is planned without consideration of spatial heterogeneity in lung function or tumor response, which may have contributed to failed uniform dose escalation in a randomized trial. The feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [{sup 99m}Tc]MAA-SPECT/CT perfused lung while redistributing 74Gy within [{sup 18}F]FDG-PET/CT biological target volumes was assessed. Methods: Eight Stage IIB–IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain <20Gy mean lung dose (MLD). Prescriptions included 60Gy to PTV and concomitantmore » boost of 74Gy mean to biological target volumes (BTV=GTV+PET margin) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial TPS via previously reported ROI discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with VMAT, proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination PBS (avoidance) plus VMAT (escalation). Dosimetric differences were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results: PTV and normal tissue objectives were not violated in 24 FLARE RT plans. Population median of mean BTV dose was 73.7Gy (68.5–75.5Gy), mean FDG-PET peak dose was 89.7Gy (73.5–103Gy), MLD was 12.3Gy (7.5–19.6Gy), and perfused MLD was 4.8Gy (0.9–12.1Gy). VMAT achieved higher dose to the FDG-PET peak subvolume (p=0.01), while PBS delivered lower dose to lung (p<0.001). Voxelwise linear correlation between BTV dose and FDG-PET uptake was higher for VMAT (R=0.93) and PBS+VMAT (R=0.94) compared to PBS alone (R=0.89). Conclusion: FLARE RT is feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG-PET dose escalation balances target/normal tissue objective tradeoffs. These results support future testing of FLARE RT safety and efficacy within a precision radiation oncology trial. This work was supported by a Research Scholar grant from the Radiological Society of North American Research & Education Foundation.« less

[First case of lung abscess due to Yersinia pseudotuberculosis in Japan].

PubMed

Takahashi, Yoshinori; Sasabe, Jun; Maeda, Hikaru; Fujiwara, Atsushi; Yuda, Hisamichi; Yoshida, Masamichi; Taguchi, Osamu

2014-07-01

A 63-year-old previously healthy man was admitted to our hospital with diarrhea that had lasted for about 4 weeks, high fever and dyspnea. Chest computed tomography showed consolidation with a low-density area in the right middle lobe and small nodules with feeding vessels in the right upper lobe. On Day 8, a cavity was observed in the consolidation, and the lymph nodes in the mediastinum became necrotic. Yersinia pseudotuberculosis (serotype 4b) was cultured from blood, bronchial washing fluid, and lung tissue specimens. We diagnosed the lung lesions as septic pulmonary embolism caused by enterocolitis. We started treatment with tazobactam/piperacillin. It has been reported that high-dose ceftriaxone (CTRX) is effective, but CTRX at normal doses and other beta-lactams are less effective or even ineffective. Therefore, we changed to CTRX (4g/day) on Day 5, CTRX (2g/day) on Day 8, and oral cefditoren pivoxil (600 mg/day; a third-generation cephalosporin) on Day 18. Antibiotic therapy resulted in a favorable response. The patient was discharged from our hospital on day 25 in good health. To the best of our knowledge, this is the first case of a lung abscess caused by Y. pseudotuberculosis reported in Japan.

Human exposure to high natural background radiation: what can it teach us about radiation risks?

PubMed Central

Hendry, Jolyon H; Simon, Steven L; Wojcik, Andrzej; Sohrabi, Mehdi; Burkart, Werner; Cardis, Elisabeth; Laurier, Dominique; Tirmarche, Margot; Hayata, Isamu

2014-01-01

Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors. PMID:19454802

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

PubMed Central

Watanabe, Tomoya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model. PMID:28651005

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

PubMed

Watanabe, Tomoya; Nishimoto, Tetsuya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley; Feghali-Bostwick, Carol

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

Combined use of backscattered and transmitted images in x-ray personnel screening systems

NASA Astrophysics Data System (ADS)

Tracey, B.; Schiefele, Markus; Alvino, Christopher; Miller, Eric; Al-Kofani, Omar

2012-06-01

Current aviation security relies heavily on personnel screening using X-ray backscatter systems or other advanced imaging technologies. Passenger privacy concerns and screening times can be reduced through the use of low-dose twosided X-ray backscatter (Bx) systems, which also have the ability to collect transmission (Tx) X-ray. Bx images reveal objects placed on the body, such as contraband and security threats, as well as anatomical features at or close to the surface, such as lungs cavities and bones. While the quality of the transmission images is lower than medical imagery due to the low X-ray dose, Tx images can be of significant value in interpreting features in the Bx images, such as lung cavities, which can cause false alarms in automated threat detection (ATD) algorithms. Here we demonstrate an ATD processing chain fusing both Tx and BX images. The approach employs automatically extracted fiducial points on the body and localized active contour methods to segments lungs in acquired Tx and Bx images. Additionally, we derive metrics from the Tx image can be related to the probability of observing internal body structure in the Bx image. The combined use of Tx and Bx data can enable improved overall system performance.

GTV-based prescription in SBRT for lung lesions using advanced dose calculation algorithms.

PubMed

Lacornerie, Thomas; Lisbona, Albert; Mirabel, Xavier; Lartigau, Eric; Reynaert, Nick

2014-10-16

The aim of current study was to investigate the way dose is prescribed to lung lesions during SBRT using advanced dose calculation algorithms that take into account electron transport (type B algorithms). As type A algorithms do not take into account secondary electron transport, they overestimate the dose to lung lesions. Type B algorithms are more accurate but still no consensus is reached regarding dose prescription. The positive clinical results obtained using type A algorithms should be used as a starting point. In current work a dose-calculation experiment is performed, presenting different prescription methods. Three cases with three different sizes of peripheral lung lesions were planned using three different treatment platforms. For each individual case 60 Gy to the PTV was prescribed using a type A algorithm and the dose distribution was recalculated using a type B algorithm in order to evaluate the impact of the secondary electron transport. Secondly, for each case a type B algorithm was used to prescribe 48 Gy to the PTV, and the resulting doses to the GTV were analyzed. Finally, prescriptions based on specific GTV dose volumes were evaluated. When using a type A algorithm to prescribe the same dose to the PTV, the differences regarding median GTV doses among platforms and cases were always less than 10% of the prescription dose. The prescription to the PTV based on type B algorithms, leads to a more important variability of the median GTV dose among cases and among platforms, (respectively 24%, and 28%). However, when 54 Gy was prescribed as median GTV dose, using a type B algorithm, the variability observed was minimal. Normalizing the prescription dose to the median GTV dose for lung lesions avoids variability among different cases and treatment platforms of SBRT when type B algorithms are used to calculate the dose. The combination of using a type A algorithm to optimize a homogeneous dose in the PTV and using a type B algorithm to prescribe the median GTV dose provides a very robust method for treating lung lesions.

A Novel Fast Helical 4D-CT Acquisition Technique to Generate Low-Noise Sorting Artifact–Free Images at User-Selected Breathing Phases

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

Thomas, David, E-mail: dhthomas@mednet.ucla.edu; Lamb, James; White, Benjamin

2014-05-01

Purpose: To develop a novel 4-dimensional computed tomography (4D-CT) technique that exploits standard fast helical acquisition, a simultaneous breathing surrogate measurement, deformable image registration, and a breathing motion model to remove sorting artifacts. Methods and Materials: Ten patients were imaged under free-breathing conditions 25 successive times in alternating directions with a 64-slice CT scanner using a low-dose fast helical protocol. An abdominal bellows was used as a breathing surrogate. Deformable registration was used to register the first image (defined as the reference image) to the subsequent 24 segmented images. Voxel-specific motion model parameters were determined using a breathing motion model. Themore » tissue locations predicted by the motion model in the 25 images were compared against the deformably registered tissue locations, allowing a model prediction error to be evaluated. A low-noise image was created by averaging the 25 images deformed to the first image geometry, reducing statistical image noise by a factor of 5. The motion model was used to deform the low-noise reference image to any user-selected breathing phase. A voxel-specific correction was applied to correct the Hounsfield units for lung parenchyma density as a function of lung air filling. Results: Images produced using the model at user-selected breathing phases did not suffer from sorting artifacts common to conventional 4D-CT protocols. The mean prediction error across all patients between the breathing motion model predictions and the measured lung tissue positions was determined to be 1.19 ± 0.37 mm. Conclusions: The proposed technique can be used as a clinical 4D-CT technique. It is robust in the presence of irregular breathing and allows the entire imaging dose to contribute to the resulting image quality, providing sorting artifact–free images at a patient dose similar to or less than current 4D-CT techniques.« less