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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort is planned.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography

Purpose: To investigate the efficacy of a new family of measurements made on individual pulmonary cysts extracted from computed tomography (CT) for assessing the severity of lymphangioleiomyomatosis (LAM). Methods: CT images were analyzed using thresholding to identify a cystic region of interest from chest CT of LAM patients. Individual cysts were then extracted from the cystic region by the watershed algorithm, which separates individual cysts based on subtle edges within the cystic regions. A family of measurements were then computed, which quantify the amount, distribution, and boundary appearance of the cysts. Sequential floating feature selection was used to select a small subset of features for quantification of the severity of LAM. Adjusted R{sup 2} from multiple linear regression and R{sup 2} from linear regression against measurements from spirometry were used to compare the performance of our proposed measurements with currently used density based CT measurements in the literature, namely, the relative area measure and the D measure. Results: Volumetric CT data, performed at total lung capacity and residual volume, from a total of 49 subjects enrolled in the MILES trial were used in our study. Our proposed measures had adjusted R{sup 2} ranging from 0.42 to 0.59 when regressing against the spirometry measures, with p < 0.05. For previously used density based CT measurements in the literature, the best R{sup 2} was 0.46 (for only one instance), with the majority being lower than 0.3 or p > 0.05. Conclusions: The proposed family of CT-based cyst measurements have better correlation with spirometric measures than previously used density based CT measurements. They show potential as a sensitive tool for quantitatively assessing the severity of LAM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Computer-aided pulmonary image analysis in small animal models

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-BRA-09: Towards an Optimal Breath-Holding Procedure for Radiotherapy: Differences in Organ Motion During Inhalation and Exhalation Breath-Holds

Purpose: Breath-holding (BH) is often used to reduce organ motion during radiotherapy. The aim of this study was to determine the differences in pancreatic and diaphragmatic motion during BH between inhalation and exhalation BHs with variable lung volumes and to investigate whether motion increases/decreases during BH. Methods: Sixteen healthy volunteers were asked to perform four different 60-second BHs, from fully inflated to fully deflated lungs (i.e. lung volumes of: 100%, ∼70%, ∼30% and 0% of inspiratory capacity) three times (total of 192 BHs). During each BH, we obtained single-slice (coronal) magnetic-resonance scans with spatial resolution 0.93×0.93×8.0 mm3 and temporal resolution 0.6 s. We used 2-dimensional image correlation to obtain the motion of pancreatic head and diaphragm during BH. Motion magnitude in inferior-superior direction was obtained by determining the maximum displacement during BH. Results: Pancreatic and diaphragmatic drifts occurred during BH and were mostly in the superior direction. We observed significantly smaller pancreatic and diaphragmatic motion magnitudes in inferior-superior direction during exhalation BHs (BH{sub 30%} and BH{sub 0%}) compared to inhalation BHs (BH{sub 100%} and BH{sub 70%}). The mean motion magnitudes of the pancreatic head were 7.0, 6.5, 4.4 and 4.2 mm during BH{sub 100%}, BH{sub 70%}, BH{sub 30%} and BH{sub 0%}, respectively, and mean BH durations were 59.9, 59.1, 59.0 and 52.7 s. For the diaphragm, mean motion magnitudes were 9.8, 9.0, 5.6 and 4.3 mm, respectively. When considering 30-second BHs, as often used in the clinic, the motion was most pronounced during the first 10 s and excluding these from the analysis (yielding an effective BH period of 20 s) significantly reduced (P≤0.002) organ motion. Conclusion: Organ motion was significantly smaller during exhalation BHs compared to inhalation BHs. Also, motion was largest at the start of BH. Hence, waiting for 10 s may significantly decrease motion of the pancreas and diaphragm during treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into “biomimetic” nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.

36 MATERIALS SCIENCE↗
DOE OSTI2015

Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon

Purpose: Inefficient T-cell reconstitution from x-ray–induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response. Methods and Materials: CD3{sup +}, CD8{sup +}, and CD4{sup +} T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice. Results: Reconstitution of CD4{sup +} T cells was delayed more than that of CD8{sup +} T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model. Conclusions: T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the proliferation of Th1 and by suppressing expansions of Th17 and Tregs. The role of cinnamon in efficient T-cell reconstitution from SLTBI is effective in antitumor immunity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-P-19: A National Collaborative Academic Medical Physics Network: Structure, Activity and Outcomes

Purpose: A national Australian inter-university medical physics (MP) group was formed in 2011/12, supported by Department of Health Better Access to Radiation Oncology BARO) seed funding. Core membership includes the six universities providing postgraduate MP courses. Objectives include increasing capacity, development and efficiency of national academic MP structures/systems and hence supporting education, clinical training and research, for the MP workforce support. Although the BARO scheme focuses on Radiation Oncology, the group has wider MP interests. Methods: Two further BARO seed grants were achieved: 1) for networked academic activities, including shared-resource teaching, eg using virtual reality systems; MP outreach to schools and undergraduates; developing web-based student and registrar education/resources, etc.; and 2) for conjoint ‘translational research’ posts between universities and partner hospitals, to clinically progress advanced RT technologies and to support students and registrars. Each university received 0.5 FTE post from each grant over 2 years (total: $1.75M) and leveraged local additional partner funds. Results: Total funding: $4–5M. Overall there have been 35 (mainly overseas) postholders bringing specific expertise, beginning in early 2013. Periods in Australia have been from 0.25–2 years (median=1). As well as the education activities, research projects include lung/spine SBRT, 4D RT, FFF beams, technology assessment, complex treatment planning, imaging for radiation oncology, DIR, adaptive breast, datamining, radiomics,etc. Observed positive impacts include: increased interest in MP courses, training support, translational research infrastructure and/or clinical practice in the hospitals involved, plus increased collaboration and effectiveness between the universities. Posts are continuing beyond grant end using leveraged funds, providing the basis for sustainability of some posts. Conclusion: The BARO-funded projects have cost-effectively produced a range of positive impacts on training, research and practice in hospitals and between universities. The evaluation of the specific post roles and activities, and their outcomes, has produced focused recommendations on continuation and sustainability. Funding was from the Australian federal Department of Health; leveraged funding was from partner universities and hospitals.

60 APPLIED LIFE SCIENCES↗