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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Emulating the Lyman-Alpha forest 1D power spectrum from cosmological simulations: new models and constraints from the eBOSS measurement

We present the Lyssa suite of high-resolution cosmological simulations of the Lyman-α forest designed for cosmological analyses. These 18 simulations have been run using the Nyx code with 40963 hydrodynamical cells in a 120 Mpc (∼ 81 Mpc/h) comoving box and individually provide sub-percent level convergence of the Lyman-α forest 1d flux power spectrum. We build a Gaussian process emulator for the Lyssa simulations in the lym1d likelihood framework to interpolate the power spectrum at arbitrary parameter values. We validate this emulator based on leave-one-out tests and based on the parameter constraints for simulations outside of the training set. We also perform comparisons with a previous emulator, showing a percent level accuracy and a good recovery of the expected cosmological parameters. Using this emulator we derive constraints on the linear matter power spectrum amplitude and slope parameters A Lyα and n Lyα . While the best-fit Planck ΛCDM model has A Lyα = 8.79 and n Lyα = -2.363, from DR14 eBOSS data we find that A Lyα < 7.6 (95% CI) and n Lyα = -2.369 ± 0.008. The low value of A Lyα , in tension with Planck, is driven by the correlation of this parameter with the mean transmission of the Lyman-α forest. This tension disappears when imposing a well-motivated external prior on this mean transmission, in which case we find A Lyα = 9.8 ± 1.1 in accordance with Planck.

Walther, Michael↗
NASA NTRS1982

Integral dependent spin couplings in CI calculations

Although the number of ways to combine Slater determinants to form spin eigenfunctions increases rapidly with the number of open shells, most of these spin couplings will make only a small contribution to a given state, provided the spin coupling is chosen judiciously. The technique of limiting calculations to the interacting subspace pioneered by Bunge (1970) was employed by Munch and Davidson (1975) to the vanadium atom. The use of an interacting space looses its advantage in more complex cases. However, the problem can always be reduced to only one interacting spin coupling by making the coefficients integral dependent. The present investigation is concerned with the performance of integral dependent interacting couplings, taking into account the results of three test calculations.

Iberle, K.↗
NASA NTRS2001

Assessment of internal mammary artery and saphenous vein graft patency and flow reserve using transthoracic Doppler echocardiography

OBJECTIVE: To investigate transthoracic Doppler echocardiography in the identification of coronary artery bypass graft (CABG) flow for assessing graft patency. DESIGN: The initial study group comprised 45 consecutive patients with previous CABG undergoing elective cardiac catheterisation for recurrent ischaemia. The Doppler variables best correlated with angiographic graft patency were then tested prospectively in a further 84 patients (test group). SETTING: Three tertiary referral centres. INTERVENTIONS: Flow velocities in grafts were recorded at rest and during hyperaemia induced by dipyridamole (0.56 mg/kg/4 min), under the guidance of transthoracic colour Doppler flow mapping. Findings on transthoracic Doppler were compared with angiography. MAIN OUTCOME MEASURES: Feasibility of identifying open grafts by Doppler and diagnostic accuracy for Doppler detection of significant (>/= 70%) graft stenosis. RESULTS: In the test group the identification rate for mammary artery grafts was 100%, for saphenous vein grafts to left anterior descending coronary artery 91%, for vein grafts to right coronary artery 96%, and for vein grafts to circumflex artery 90%. Coronary flow reserve (the ratio between peak diastolic velocity under hyperaemia and at baseline) of < 1.9 (95% confidence interval 1.83 to 2.08) had 100% sensitivity, 98% specificity, 87.5% positive predictive value, and 100% negative predictive value for mammary artery graft stenosis. Coronary flow reserve of < 1.6 (95% CI 1.51 to 1.73) had 91% sensitivity, 87% specificity, 85.4% positive predictive value, and 92.3% negative predictive value for significant vein graft stenosis. CONCLUSIONS: Transthoracic Doppler can provide non-invasive assessment of CABG patency.

Multicenter Study↗
DOE OSTI2020

MAFLD identifies patients with significant hepatic fibrosis better than NAFLD

Abstract Background & Aims Diagnostic criteria for metabolic associated fatty liver disease (MAFLD) have been proposed, but not validated. We aimed to compare the diagnostic accuracy of the MAFLD definition vs the existing NAFLD criteria to identify patients with significant fibrosis and to characterize the impact of mild alcohol intake. Methods We enrolled 765 Japanese patients with fatty liver (median age 54 years). MAFLD and NAFLD were diagnosed in 79.6% and 70.7% of patients respectively. Significant fibrosis was defined by FIB‐4 index ≥1.3 and liver stiffness ≥6.6 kPa using shear wave elastography. Mild alcohol intake was defined as <20 g/day. Factors associated with significant fibrosis were analysed by logistic regression and decision‐tree analyses. Results Liver stiffness was higher in MAFLD compared to NAFLD (7.7 vs 6.8 kPa, P = .0010). In logistic regression, MAFLD (OR 4.401; 95% CI 2.144‐10.629; P < .0001), alcohol intake (OR 1.761; 95% CI 1.081‐2.853; P = .0234), and NAFLD (OR 1.721; 95%CI 1.009‐2.951; P = .0463) were independently associated with significant fibrosis. By decision‐tree analysis, MAFLD, but not NAFLD or alcohol consumption was the initial classifier for significant fibrosis. The sensitivity for detecting significant fibrosis was higher for MAFLD than NAFLD (93.9% vs 73.0%). In patients with MAFLD, even mild alcohol intake was associated with an increase in the prevalence of significant fibrosis (25.0% vs 15.5%; P = .0181). Conclusions The MAFLD definition better identifies a group with fatty liver and significant fibrosis evaluated by non‐invasive tests. Moreover, in patients with MAFLD, even mild alcohol consumption is associated with worsening of hepatic fibrosis measures.

Yamamura, Sakura↗
DOE OSTI2018

Radioembolization Super Survivors: Extended Survival in Non-operative Hepatocellular Carcinoma

PurposeTo identify baseline characteristics and long-term prognostic factors in non-transplant patients with unresectable hepatocellular carcinoma (HCC) who had prolonged survival after treatment with yttrium-90 radioembolization (Y90).Materials and MethodsSixty-seven “Super Survivors” (defined as ≥ 3-year survival after Y90) were identified within our 1000-patient Y90 database (2003–2017). Baseline imaging and follow-up occurred at 1 month and every 3 months thereafter. Overall survival (OS) was calculated with Kaplan–Meier estimates with log-rank test in subgroups: Child–Pugh (CP) score, distribution of disease, portal vein thrombus (PVT), and technique (segmental vs lobar Y90).Results Median age 69.5 years (range 45–94 years); 69% male; 60% solitary HCC; 79% unilobar disease; 12% PVT; 10% ascites; Barcelona Clinic Liver Cancer Stage A—54%/B—28%/C—16%/D—2%; CP A—70%/B—28%/C—2%. Longest baseline tumor diameter was 5.4 ± 4.0 cm (mean ± SD). All patients had an imaging response (either partial or complete response). Median OS was 67.5 months (95% CI 55.2–82.5). CP score and main PVT stratified median OS (p = 0.0007 and p = 0.0187, respectively). Beyond 3 years, segmental versus lobar Y90 was associated with improved OS with a median OS of 80.2 versus 46.7 months, respectively (p = 0.0024). Dosing > 200 Gy was not a significant predictor of improved OS.ConclusionsSuper Survivors spanning the BCLC staging system maintained durable OS after radioembolization that was stratified by the extent of underlying liver disease. The common variable among all patients was an imaging response. Segmental versus lobar Y90 may have a long-term associated OS benefit.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-R-51: Radiomics in CT Perfusion Maps of Head and Neck Cancer

Purpose: The aim of this study was to test the predictive value of radiomics features of CT perfusion (CTP) for tumor control, based on a preselection of radiomics features in a robustness study. Methods: 11 patients with head and neck cancer (HNC) and 11 patients with lung cancer were included in the robustness study to preselect stable radiomics parameters. Data from 36 HNC patients treated with definitive radiochemotherapy (median follow-up 30 months) was used to build a predictive model based on these parameters. All patients underwent pre-treatment CTP. 315 texture parameters were computed for three perfusion maps: blood volume, blood flow and mean transit time. The variability of texture parameters was tested with respect to non-standardizable perfusion computation factors (noise level and artery contouring) using intraclass correlation coefficients (ICC). The parameter with the highest ICC in the correlated group of parameters (inter-parameter Spearman correlations) was tested for its predictive value. The final model to predict tumor control was built using multivariate Cox regression analysis with backward selection of the variables. For comparison, a predictive model based on tumor volume was created. Results: Ten parameters were found to be stable in both HNC and lung cancer regarding potentially non-standardizable factors after the correction for inter-parameter correlations. In the multivariate backward selection of the variables, blood flow entropy showed a highly significant impact on tumor control (p=0.03) with concordance index (CI) of 0.76. Blood flow entropy was significantly lower in the patient group with controlled tumors at 18 months (p<0.1). The new model showed a higher concordance index compared to the tumor volume model (CI=0.68). Conclusion: The preselection of variables in the robustness study allowed building a predictive radiomics-based model of tumor control in HNC despite a small patient cohort. This model was found to be superior to the volume-based model. The project was supported by the KFSP Tumor Oxygenation of the University of Zurich, by a grant of the Center for Clinical Research, University and University Hospital Zurich and by a research grant from Merck (Schweiz) AG.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). To study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2024

Bulk Major and Trace Elemental Composition of an Aggregate Sample From Asteroid Bennu

On September 24, 2023, NASA’s OSIRIS-REx mission returned a capsule to Earth carrying material from asteroid Bennu. This event was the first time a U.S. mission delivered pristine samples from an asteroid and is the largest asteroid sample return to date. As these samples represent some of the oldest, most primitive, and pristine materials available to us, and which originate from a known and well-studied asteroid, they allow us a rare opportunity to gain a better understanding of the formation and evolution of our solar system. Key to understanding the material returned from asteroid Bennu is establishing its bulk chemical composition. Previous studies have shown that each chondrite group has a distinct elemental composition. For the carbonaceous chondrites specifically, each group exhibits a distinct pattern of moderately and highly volatile elemental depletions, relative to CI chondrites. CI chondrites are considered the most primitive chondrite group and broadly represent the solar photosphere composition. The two most striking features of these depletion patterns is that the moderately volatile element depletions increase with decreasing 50% condensation temperature and then plateau out at abundances that roughly correlate with matrix abundance. Due to these distinctive patterns, bulk elemental composition has become an important classification tool for establishing the different chondrite groups and the connections between them. As such, determining the bulk chemical composition of the Bennu aggregates will help to test two mission hypothesis: “Bennu’s bulk elemental composition reflects that of its main parent asteroid and is similar to the composition of the Sun, with depletions in moderately to highly volatile elements” and “Bennu’s dominant lithologies are comparable in bulk mineralogy, petrology, and composition to the most aqueously altered carbonaceous chondrites” . Furthermore as the carbonaceous and non-carbonaceous chondrites are thought to have likely formed in the inner and outer protoplanetary disk, respectively (e.g., [8]), determining the bulk chemical compositions of the Bennu aggregates will also help test the major mission hypothesis that “Bennu's parent body formed beyond the snow line by accretion of material in the pro-toplanetary disk” . Regarding chondrite formation, observed elemental patterns have been successfully used to model how the mixing of volatile-rich and volatile-poor chondritic components can produce the observed carbonaceous chondrites groups. They have also been significant in investigating how volatilization processes influenced chondrite formation. As such, establishing bulk chemical compositions of the pristine Bennu samples is vital for understanding the asteroid, and solar system formation. To begin this processes, we analyzed the bulk major and trace elemental compositions of Bennu aggregates.

P Koefoed↗
DOE OSTI2015

Knowledge-based prediction of plan quality metrics in intracranial stereotactic radiosurgery

Purpose: The objective of this work was to develop a comprehensive knowledge-based methodology for predicting achievable dose–volume histograms (DVHs) and highly precise DVH-based quality metrics (QMs) in stereotactic radiosurgery/radiotherapy (SRS/SRT) plans. Accurate QM estimation can identify suboptimal treatment plans and provide target optimization objectives to standardize and improve treatment planning. Methods: Correlating observed dose as it relates to the geometric relationship of organs-at-risk (OARs) to planning target volumes (PTVs) yields mathematical models to predict achievable DVHs. In SRS, DVH-based QMs such as brain V{sub 10Gy} (volume receiving 10 Gy or more), gradient measure (GM), and conformity index (CI) are used to evaluate plan quality. This study encompasses 223 linear accelerator-based SRS/SRT treatment plans (SRS plans) using volumetric-modulated arc therapy (VMAT), representing 95% of the institution’s VMAT radiosurgery load from the past four and a half years. Unfiltered models that use all available plans for the model training were built for each category with a stratification scheme based on target and OAR characteristics determined emergently through initial modeling process. Model predictive accuracy is measured by the mean and standard deviation of the difference between clinical and predicted QMs, δQM = QM{sub clin} − QM{sub pred}, and a coefficient of determination, R{sup 2}. For categories with a large number of plans, refined models are constructed by automatic elimination of suspected suboptimal plans from the training set. Using the refined model as a presumed achievable standard, potentially suboptimal plans are identified. Predictions of QM improvement are validated via standardized replanning of 20 suspected suboptimal plans based on dosimetric predictions. The significance of the QM improvement is evaluated using the Wilcoxon signed rank test. Results: The most accurate predictions are obtained when plans are stratified based on proximity to OARs and their PTV volume sizes. Volumes are categorized into small (V{sub PTV} < 2 cm{sup 3}), medium (2 cm{sup 3} < V{sub PTV} < 25 cm{sup 3}), and large (25 cm{sup 3} < V{sub PTV}). The unfiltered models demonstrate the ability to predict GMs to ∼1 mm and fractional brain V{sub 10Gy} to ∼25% for plans with large V{sub PTV} and critical OAR involvements. Increased accuracy and precision of QM predictions are obtained when high quality plans are selected for the model training. For the small and medium V{sub PTV} plans without critical OAR involvement, predictive ability was evaluated using the refined model. For training plans, the model predicted GM to an accuracy of 0.2 ± 0.3 mm and fractional brain V{sub 10Gy} to 0.04 ± 0.12, suggesting highly accurate predictive ability. For excluded plans, the average δGM was 1.1 mm and fractional brain V{sub 10Gy} was 0.20. These δQM are significantly greater than those of the model training plans (p < 0.001). For CI, predictions are close to clinical values and no significant difference was observed between the training and excluded plans (p = 0.19). Twenty outliers with δGM > 1.35 mm were identified as potentially suboptimal, and replanning these cases using predicted target objectives demonstrates significant improvements on QMs: on average, 1.1 mm reduction in GM (p < 0.001) and 23% reduction in brain V{sub 10Gy} (p < 0.001). After replanning, the difference of δGM distribution between the 20 replans and the refined model training plans was marginal. Conclusions: The results demonstrate the ability to predict SRS QMs precisely and to identify suboptimal plans. Furthermore, the knowledge-based DVH predictions were directly used as target optimization objectives and allowed a standardized planning process that bettered the clinically approved plans. Full clinical application of this methodology can improve consistency of SRS plan quality in a wide range of PTV volume and proximity to OARs and facilitate automated treatment planning for this critical treatment site.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

A Mobile Hot Cell for Conditioning Disused Sealed Radioactive Sources for Storage or Transportation

An innovative Mobile Hot Cell (MHC) has been developed for conditioning Disused Sealed Radioactive Sources (DSRS) category 1 and 2 for storage or transportation. The MHC is designed to provide both Radiological and Biological containment with a maximum capacity of 1000 Ci Co60 or 5000Ci Cs137 source and can be transported via standard cargo containers. This project has been supported through the National Nuclear Safety Administration (NNSA) Offsite Source Recovery Program (OSRP). The project is intended for the international community rather than domestic although domestic use is a possibility. Many countries have significant stockpiles of these devices that are often stored in less-than-optimal circumstances. This necessitates that these devices be addressed expeditiously, and the sources secured. The MHC utilizes robotics, automation, and other non-traditional methods for disassembling, characterizing, and packaging these sources that have reached end of life or are otherwise not needed. These innovative approaches are necessary to facilitate an expedited timeline to efficiently and safely secure these sources in a non-proliferation effort. Conditioning efforts include disassembling the device such as a teletherapy head used for cancer treatment, or blood/research irradiators such that the radioactive sources may be removed safely. The sources are then characterized. Leak checks are performed, dimensions are verified, and serial numbers are confirmed. Upon completion, the sources are typically placed into a Standard Forms Capsule which is seal welded closed. It is leak tested and placed into a Long-Term Storage Shield (LTSS) which can either be secured for storage directly or loaded into an appropriate cask for transportation. Further innovations include multiple deployment scenarios that include a full deployment of MHC components, deployment of the MHC automation internal components to an existing hot cell, deployment of minimally required MHC components and incorporation of sand for shielding, and integration of the MHC for Silo Storage, or Bore Hole Storage efforts. The MHC has evolved from a very specific use case to a “Swiss Army Knife” type of a tool in that it can be readily adapted to a large variety of situations. Innovative approaches such as the use of robotics, Computer Numeric Control (CNC) machining centers, automated welding equipment, HDMI Cameras, and LED lighting are some of the developed technologies incorporated into the MHC design. Shielding is accomplished with a steel walled Base Box which is surrounded by four nesting doll shield shells which when combined limits the external dose rate to 5mr/hr when a 1000 Ci Co60 source is exposed inside.

99 - GENERAL AND MISCELLANEOUS↗
DOE OSTI2014

A National Survey of Skin Infections, Care Behaviors and MRSA Knowledge in the United States

A nationally representative sample of approximately 2000 individuals was surveyed to assess SSTI infections over their lifetime and then prospectively over six-months. Knowledge of MRSA, future likelihood to self-treat a SSTI and self-care behaviors was also queried. Chi square tests, linear and multinomial regression were used for analysis. About 50% of those with a reported history of a SSTI typical of MRSA had sought medical treatment. MRSA knowledge was low: 28% of respondents could describe MRSA. Use of protective self-care behaviors that may reduce transmission, such as covering a lesion, differed with knowledge of MRSA and socio-demographics. Those reporting a history of a MRSA-like SSTI were more likely to respond that they would self-treat than those without such a history (OR 2.05 95% CI 1.40, 3.01; p<0.001). Since half of respondents reported not seeking care for past lesions, incidence determined from clinical encounters would greatly underestimate true incidence. MRSA knowledge was not associated with seeking medical care, but was associated with selfcare practices that may decrease transmission.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Granger Causality for prediction in Dynamic Mode Decomposition: Application to power systems

Here, the dynamic mode decomposition (DMD) technique extracts the dominant modes characterizing the innate dynamical behavior of the system within the measurement data. For appropriate identification of dominant modes from the measurement data, the DMD algorithm necessitates ensuring the quality of the input measurement data sequences. On that account, for validating the usability of the dataset for the DMD algorithm, the paper proposed two conditions: Persistence of excitation (PE) and the Granger Causality Test (GCT). The virtual data sequences are designed with the hankel matrix representation such that the dimensions of the subspace spanning the essential system modes are increased with the addition of new state variables. The PE condition provides the lower bound for the trajectory length, and the GCT provides the order of the model. Satisfying the PE condition enables estimating an approximate linear model, but the predictability with the identified model is only assured with the temporal causation among data searched with GCT. The proposed methodology is validated with the application for coherency identification (CI) in a multi-machine power system (MMPS), an essential phenomenon in transient stability analysis. The significance of PE condition and GCT is demonstrated through various case studies implemented on 22 bus six generator system.

24 POWER TRANSMISSION AND DISTRIBUTION↗
NASA NTRS1994

On The Choice of a Zeroth-Order Hamiltonian for Second-Order Perturbation Theory with A CASSCF Reference Function

A new approach to perturbation theory based on a CASSCF reference function has been developed. The key to the approach is the definition of the zeroth order Hamiltonian, H(sub 0), which includes the full CI Hamiltonian for the active space. In the the inactive and secondary spaces, operators may be chosen which reduce to the usual Moller-Plesset or Epstein-Nesbet forms in the limit of a null active space. These operators are diagonal in the orbital indices and permit the block-diagonalization of H(sub 0). The reference is an eigenfunction of Ho without N-particle projection. H(sub 0) automatically incorporates denominator shifts in the style of those appearing in recent open-shell perturbation theories. Comparative results are presented for a few test cases.

Dyall, Kenneth G.↗
DOE OSTI2019

Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis

Background: The current diagnosis of infective endocarditis (IE) is based on the modified Duke criteria, which has approximately 80% sensitivity for the diagnosis of native valve endocarditis (NVE), with lower sensitivity for the diagnosis of prosthetic valve endocarditis (PVE) and culture-negative endocarditis. There is preliminary evidence that {sup 18}F-FDG PET/CT is an adjunctive diagnostic test with high accuracy reported in small studies to date. We therefore performed a meta-analysis of studies evaluating the use of PET/CT in the diagnosis of IE to establish a more precise estimate of accuracy. Methods: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov were searched from January 1990 to April 2017 for studies evaluating the accuracy of PET/CT for the evaluation of possible IE. Results: We identified 13 studies involving 537 patients that were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of IE was 76.8% (95% CI 71.8–81.4%; Q = 39.9, P < 0.01; I{sup 2} = 69.9%) and the pooled specificity was 77.9% (95% CI 71.9–83.2%; Q = 44.42, P < 0.01; I{sup 2} = 73.0%). Diagnostic accuracy was improved for PVE with sensitivity of 80.5% (95% CI 74.1–86.0%; Q = 25.5, P < 0.01; I{sup 2} = 72.5%) and specificity of 73.1% (95% CI 63.8–81.2%; Q = 32.1, P < 0.01; I{sup 2} = 78.2%). Additional extracardiac foci of infection were found on 17% of patients on whole body PET/CT. Conclusion: PET/CT is a useful adjunctive diagnostic tool in the evaluation of diagnostically challenging cases of IE, particularly in prosthetic valve endocarditis. It also has the potential to detect clinically relevant extracardiac foci of infection, malignancy, and other sources of inflammation leading to more appropriate treatment regimens and surgical intervention.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Validation of High-Risk Computed Tomography Features for Detection of Local Recurrence After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Purpose: Fibrotic changes after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are difficult to distinguish from local recurrences (LR), hampering proper patient selection for salvage therapy. This study validates previously reported high-risk computed tomography (CT) features (HRFs) for detection of LR in an independent patient cohort. Methods and Materials: From a multicenter database, 13 patients with biopsy-proven LR were matched 1:2 to 26 non-LR control patients based on dose, planning target volume (PTV), follow-up time, and lung lobe. Tested HRFs were enlarging opacity, sequential enlarging opacity, enlarging opacity after 12 months, bulging margin, linear margin disappearance, loss of air bronchogram, and craniocaudal growth. Additionally, 2 new features were analyzed: the occurrence of new unilateral pleural effusion, and growth based on relative volume, assessed by manual delineation. Results: All HRFs were significantly associated with LR except for loss of air bronchogram. The best performing HRFs were bulging margin, linear margin disappearance, and craniocaudal growth. Receiver operating characteristic analysis of the number of HRFs to detect LR had an area under the curve (AUC) of 0.97 (95% confidence interval [CI] 0.9-1.0), which was identical to the performance described in the original report. The best compromise (closest to 100% sensitivity and specificity) was found at ≥4 HRFs, with a sensitivity of 92% and a specificity of 85%. A model consisting of only 2 HRFs, bulging margin and craniocaudal growth, resulted in a sensitivity of 85% and a specificity of 100%, with an AUC of 0.96 (95% CI 0.9-1.0) (HRFs ≥2). Pleural effusion and relative growth did not significantly improve the model. Conclusion: We successfully validated CT-based HRFs for detection of LR after SBRT for early-stage NSCLC. As an alternative to number of HRFs, we propose a simplified model with the combination of the 2 best HRFs: bulging margin and craniocaudal growth, although validation is warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC. Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Investigating effects of soil chemicals on density of small mammal bioindicators using spatial capture-recapture models

Monitoring the ecological impacts of environmental pollution and the effectiveness of remediation efforts requires identifying relationships between contaminants and the disruption of biological processes in populations, communities, or ecosystems. Wildlife are useful bioindicators, but traditional comparative experimental approaches rely on a staunch and typically unverifiable assumption that, in the absence of contaminants, reference and contaminated sites would support the same densities of bioindicators, thereby inferring direct causation from indirect data. We demonstrate the utility of spatial capture-recapture (SCR) models for overcoming these issues, testing if community density of common small mammal bioindicators was directly influenced by soil chemical concentrations. By modeling density as an inhomogeneous Poisson point process, we found evidence for an inverse spatial relationship between Peromyscus density and soil mercury concentrations, but not other chemicals, such as polychlorinated biphenyls, at a site formerly occupied by a nuclear reactor. Although the coefficient point estimate supported Peromyscus density being lower where mercury concentrations were higher (β = –0.44), the 95% confidence interval overlapped zero, suggesting no effect was also compatible with our data. Estimated density from the most parsimonious model (2.88 mice/ha; 95% CI = 1.63–5.08), which did not support a density-chemical relationship, was within the range of reported densities for Peromyscus that did not inhabit contaminated sites elsewhere. Environmental pollution remains a global threat to biodiversity and ecosystem and human health, and our study provides an illustrative example of the utility of SCR models for investigating the effects that chemicals may have on wildlife bioindicator populations and communities.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Prenatal and postnatal polybrominated diphenyl ether exposure and visual spatial abilities in children

Polybrominated diphenyl ethers (PBDEs) are associated with impaired visual spatial abilities in toxicological studies, but no epidemiologic study has investigated PBDEs and visual spatial abilities in children. The Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003–2006, Cincinnati, OH), was used to examine prenatal and childhood PBDEs and visual spatial abilities in 199 children. PBDEs were measured at 16±3 weeks gestation and at 1, 2, 3, 5, and 8 years using gas chromatography/isotope dilution high-resolution mass spectrometry. We used the Virtual Morris Water Maze to measure visual spatial abilities at 8 years. In covariate-adjusted models, 10-fold increases in BDE-47, −99, and −100 at 5 years were associated with shorter completion times by 5.2 s (95% Confidence Interval [CI] −9.3, −1.1), 4.5 s (95% CI −8.1, −0.9), and 4.7 s (95% CI −9.0, −0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (β=5.4 s, 95% CI −0.3, 11.1). Prenatal PBDEs were associated with improved visual spatial memory retention, with children spending a higher percentage of their search path in the correct quadrant. Child sex modified some associations between PBDEs and visual spatial learning. Longer path lengths were observed among males with increased BDE-47 at 2 and 3 years, while females had shorter paths. In conclusion, prenatal and postnatal BDE-28, −47, −99, and −100 at 5 and 8 years were associated with improved visual spatial abilities, whereas a pattern of impairments in visual spatial learning was noted with early childhood BDE-153 concentrations. - Highlights: • The VMWM test was used to assess visual spatial abilities in children at 8 years. • BDE-153 at 3 years was adversely associated with visual spatial learning. • BDE-47, −99, and −100 at 5 years was associated with better visual spatial learning. • Prenatal PBDEs were associated with improved visual spatial memory retention. • Male children were observed to perform more poorly on the VMWM than females.

54 ENVIRONMENTAL SCIENCES↗