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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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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Strategies for Motion Robust Proton Therapy With Pencil Beam Scanning for Esophageal Cancer

Proton therapy of esophageal cancer is superior to photon radiation therapy in terms of normal tissue sparing. However, respiratory motion and anatomical changes may compromise target dose coverage owing to density changes, geometric misses, and interplay effects. Here we investigate the combined effect on clinical target volume (CTV) coverage and compare proton therapy with intensity modulated radiation therapy (IMRT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

A Review of Cardiac Radioablation (CR) for Arrhythmias: Procedures, Technology, and Future Opportunities

Cardiac radioablation (CR), a new treatment for cardiac arrhythmias such as ventricular tachycardia and atrial fibrillation, has had promising clinical outcomes to date. There is consequent desire for rapid clinical adoption. However, CR presents unique challenges to radiation therapy, and it is paramount that clinical adoption be performed safely and effectively. Recent reviews comprehensively detail patient selection, clinical history, treatment outcomes, and treatment toxicities but only briefly mention the technical aspects of CR. To address this knowledge gap, this review collates currently available knowledge regarding CR technology choice and procedural details to help inform and guide clinics considering implementing their own CR program, to aid technique standardization, and to highlight areas that require further development or verification.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

Herein, a copper-mediated radiobromination of (hetero)aryl boronic pinacol esters is described. Cyclotron-produced [76/77Br]bromide was isolated using an anion exchange cartridge, wherein the pre-equilibration and elution solutions played a critical role in downstream deboro-bromination. The bromination tolerates a broad range of functional groups, labeling molecules with ranging electronic and steric effects. Bologically active radiopharmaceuticals were synthesized, including two radiobrominated inhibitors of poly ADP ribose polymerase, a clinically relevant chemotherapeutic target for ovarian, breast, and prostate cancers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Many-isocenter optimization for robotic radiotherapy

Despite significant dosimetric gains, clinical implementation of the 4π non-coplanar radiotherapy on the widely available C-arm gantry system is hindered by limited clearance, and the need to perform complex coordinated gantry and couch motion. A robotic radiotherapy platform would be conducive to such treatment but a new conflict between field size and MLC modulation resolution needs to be managed for versatile applications. This study investigates the dosimetry and delivery efficiency of purposefully creating many isocenters to achieve simultaneously high MLC modulation resolution and large tumor coverage. An integrated optimization framework was proposed for simultaneous beam orientation optimization (BOO), isocenter selection, and fluence map optimization (FMO). The framework includes a least-square dose fidelity objective, a total variation term for regularizing the fluence smoothness, and a group sparsity term for beam selection. A minimal number of isocenters were identified for efficient target coverage. Colliding beams excluded, high-resolution small-field 4π intensity-modulated radiotherapy (IMRT) treatment plans with 50 cm source-to-isocenter distance (SID-50) on 10 Head and Neck (H&N) cancer patients were compared with low-resolution large-field plans with 100 cm SID (SID-100). With the same or better target coverage, the average reduction of [Dmean, Dmax] of 20-beam SID-50 plans from 20-beam SID-100 plans were [2.09 Gy, 1.19 Gy] for organs at risk (OARs) overall, [3.05 Gy, 0.04 Gy] for parotid gland, [3.62 Gy, 5.19 Gy] for larynx, and [3.27 Gy, 1.10 Gy] for mandible. R50 and integral dose were reduced by 5.3% and 9.6%, respectively. Wilcoxon signed-rank test showed significant difference (p < 0.05) in planning target volume (PTV) homogeneity, PTV Dmax, R50, Integral dose, and OAR Dmean and Dmax. The estimated delivery time of 20-beam [SID-50, SID-100] plans were [19, 18] min and [14, 9] min, assuming 5 fractions and 30 fractions, respectively. Finally, with clinically acceptable delivery efficiency, many-isocenter optimization is dosimetrically desirable for treating large targets with high modulation resolution on the robotic platform.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Personalized and uncertainty-aware coronary hemodynamics simulations: From Bayesian estimation to improved multi-fidelity uncertainty quantification

Non-invasive simulations of coronary hemodynamics have improved clinical risk stratification and treatment outcomes for coronary artery disease, compared to relying on anatomical imaging alone. However, simulations typically use empirical approaches to distribute total coronary flow amongst the arteries in the coronary tree, which ignores patient variability, the presence of disease, and other clinical factors. Further, uncertainty in the clinical data often remains unaccounted for in the modeling pipeline. We present an end-to-end uncertainty-aware pipeline to (1) personalize coronary flow simulations by incorporating vessel-specific coronary flows as well as cardiac function; and (2) predict clinical and biomechanical quantities of interest with improved precision, while accounting for uncertainty in the clinical data. We assimilate patient-specific measurements of myocardial blood flow from clinical CT myocardial perfusion imaging to estimate branch-specific coronary artery flows. Simulated noise in the clinical data is used to estimate the joint posterior distributions of the model parameters using adaptive Markov Chain Monte Carlo sampling. Additionally, the posterior predictive distribution for the relevant quantities of interest is determined using a new approach combining multi-fidelity Monte Carlo estimation with non-linear, data-driven dimensionality reduction. This leads to improved correlations between high- and low-fidelity model outputs. Our framework accurately recapitulates clinically measured cardiac function as well as branch-specific coronary flows under measurement noise uncertainty. We observe substantial reductions in confidence intervals for estimated quantities of interest compared to single-fidelity Monte Carlo estimation and state-of-the-art multi-fidelity Monte Carlo methods. This holds especially true for quantities of interest that showed limited correlation between the low- and high-fidelity model predictions. In addition, the proposed multi-fidelity Monte Carlo estimators are significantly cheaper to compute than traditional estimators, under a specified confidence level or variance. The proposed pipeline for personalized and uncertainty-aware predictions of coronary hemodynamics is based on routine clinical measurements and recently developed techniques for CT myocardial perfusion imaging. The proposed pipeline offers significant improvements in precision and reduction in computational cost.

Bayesian parameter estimation↗
DOE OSTI2022

Development and Validation of a Non-Invasive, Chairside Oral Cavity Cancer Risk Assessment Prototype Using Machine Learning Approach

Oral cavity cancer (OCC) is associated with high morbidity and mortality rates when diagnosed at late stages. Early detection of increased risk provides an opportunity for implementing prevention strategies surrounding modifiable risk factors and screening to promote early detection and intervention. Historical evidence identified a gap in the training of primary care providers (PCPs) surrounding the examination of the oral cavity. The absence of clinically applicable analytical tools to identify patients with high-risk OCC phenotypes at point-of-care (POC) causes missed opportunities for implementing patient-specific interventional strategies. This study developed an OCC risk assessment tool prototype by applying machine learning (ML) approaches to a rich retrospectively collected data set abstracted from a clinical enterprise data warehouse. We compared the performance of six ML classifiers by applying the 10-fold cross-validation approach. Accuracy, recall, precision, specificity, area under the receiver operating characteristic curve, and recall–precision curves for the derived voting algorithm were: 78%, 64%, 88%, 92%, 0.83, and 0.81, respectively. The performance of two classifiers, multilayer perceptron and AdaBoost, closely mirrored the voting algorithm. Integration of the OCC risk assessment tool developed by clinical informatics application into an electronic health record as a clinical decision support tool can assist PCPs in targeting at-risk patients for personalized interventional care.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Comparing Individualized Survival Predictions From Random Survival Forests and Multistate Models in the Presence of Missing Data: A Case Study of Patients With Oropharyngeal Cancer

Background: In recent years, interest in prognostic calculators for predicting patient health outcomes has grown with the popularity of personalized medicine. These calculators, which can inform treatment decisions, employ many different methods, each of which has advantages and disadvantages. Methods: We present a comparison of a multistate model (MSM) and a random survival forest (RSF) through a case study of prognostic predictions for patients with oropharyngeal squamous cell carcinoma. The MSM is highly structured and takes into account some aspects of the clinical context and knowledge about oropharyngeal cancer, while the RSF can be thought of as a black-box non-parametric approach. Key in this comparison are the high rate of missing values within these data and the different approaches used by the MSM and RSF to handle missingness. Results: We compare the accuracy (discrimination and calibration) of survival probabilities predicted by both approaches and use simulation studies to better understand how predictive accuracy is influenced by the approach to (1) handling missing data and (2) modeling structural/disease progression information present in the data. We conclude that both approaches have similar predictive accuracy, with a slight advantage going to the MSM. Conclusions: Although the MSM shows slightly better predictive ability than the RSF, consideration of other differences are key when selecting the best approach for addressing a specific research question. These key differences include the methods’ ability to incorporate domain knowledge, and their ability to handle missing data as well as their interpretability, and ease of implementation. Ultimately, selecting the statistical method that has the most potential to aid in clinical decisions requires thoughtful consideration of the specific goals.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2010

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗
DOE OSTI2021

Salivary and Dental Complications in Childhood Cancer Survivors Treated With Radiation Therapy to the Head and Neck: A Pediatric Normal Tissue Effects in the Clinic (PENTEC) Comprehensive Review

Radiation therapy (RT) to the head and neck (H&N) region is critical in the management of various pediatric malignancies; however, it may result in late toxicity. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on salivary dysfunction and dental abnormalities in survivors who received RT to the H&N region as children.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Translation of DNA Damage Response Inhibitors as Chemoradiation Sensitizers From the Laboratory to the Clinic

Combination therapies with agents targeting the DNA damage response (DDR) offer an opportunity to selectively enhance the therapeutic index of chemoradiation or eliminate use of chemotherapy altogether. The successful translation of DDR inhibitors to clinical use requires investigating both their direct actions as (chemo)radiosensitizers and their potential to stimulate tumor immunogenicity. Beginning with high-throughput screening using both viability and DNA damage-reporter assays, followed by validation in gold-standard radiation colony-forming assays and in vitro assessment of mechanistic effects on the DDR, we describe proven strategies and methods leading to the clinical development of DDR inhibitors both with radiation alone and in combination with chemoradiation. Beyond these in vitro studies, we discuss the impact of key features of human xenograft and syngeneic mouse models on the relevance of in vivo tumor efficacy studies, particularly with regard to the immunogenic effects of combined therapy with radiation and DDR inhibitors. Finally, we describe recent technological advances in radiation delivery (using the small animal radiation research platform) that allow for conformal, clinically relevant radiation therapy in mouse models. This overall approach is critical to the successful clinical development and ultimate Food and Drug Administration approval of DDR inhibitors as (chemo)radiation sensitizers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2021

Applying a One Health Approach in Global Health and Medicine: Enhancing Involvement of Medical Schools and Global Health Centers

Multidisciplinary and multisectoral approaches such as One Health and related concepts (e.g., Planetary Health, EcoHealth) offer opportunities for synergistic expertise to address complex health threats. The connections between humans, animals, and the environment necessitate collaboration among sectors to comprehensively understand and reduce risks and consequences on health and wellbeing. One Health approaches are increasingly emphasized for national and international plans and strategies related to zoonotic diseases, food safety, antimicrobial resistance, and climate change, but to date, the possible applications in clinical practice and benefits impacting human health are largely missing.

Catherine Machalaba↗
NASA NTRS2000

Resistance exercise countermeasures for space flight: implications of training specificity

While resistance exercise should be a logical choice for prevention of strength loss during unloading, the principle of training specificity cannot be overlooked. Our purpose was to explore training specificity in describing the effect of our constant load exercise countermeasure on isokinetic strength performance. Twelve healthy men (mean +/- SD: 28.0 +/- 5.2 years, 179.4 +/- 3.9 cm, 77.5 +/- 13.6 kg) were randomly assigned to no exercise or resistance exercise (REX) during 14 days of bed rest. REX performed five sets of leg press exercise to volitional fatigue (6-10 repetitions) every other day. Unilateral isokinetic concentric-eccentric knee extension testing performed before and on day 15 prior to reambulation included torque-velocity and power-velocity relationships at four velocities (0.52, 1.75, 2.97, and 4.19 rad s-1), torque-position relationship, and contractile work capacity (10 repetitions at 1.05 rad s-1). Two (group) x 2 (time) ANOVA revealed no group x time interactions; thus, groups were combined. Across velocities, angle-specific torque fell 18% and average power fell 20% (p < 0.05). No velocity x time or mode (concentric/eccentric) x time interactions were noted. Torque x position decreased on average 24% (p < 0.05). Total contractile work dropped 27% (p < 0.05). Results indicate bed rest induces rapid and marked reductions in strength and our constant load resistance training protocol did not prevent isokinetic strength losses. Differences between closed-chain training and open-chain testing may explain the lack of protection.

Randomized Controlled Trial↗
DOE OSTI2023

Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics

In the field of nuclear medicine, the β + -emitting 43 Sc and β - -emitting 47 Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177 Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47 Sc than for other proposed true theranostics. Before 43/47 Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope’s radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43 Sc via the 42 Ca(d,n) 43 Sc reaction has been devised, exhibiting reasonable yields. The Nat Ti(γ,p) 47 Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47 Sc. The conjugation of 43/47 Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47 Sc-PSMA-617 are also presented.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Construction of the Bioconjugate Py‐Macrodipa‐PSMA and Its In Vivo Investigations with Large 132/135 La 3+ and Small 47 Sc 3+ Radiometal Ions

To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large 132/135 La 3+ , 213 Bi 3+ , and small 44 Sc 3+ . Here, in this study, we report a 10-step organic synthesis of its bifunctional analogue py-macrodipa-NCS, which contains an amine-reactive −NCS group that is amenable for bioconjugation reactions to targeting vectors. The hydrolytic stability of py-macordipa-NCS was assessed, revealing a half-life of 6.0 d in pH 9.0 aqueous buffer. This bifunctional chelator was then conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, yielding the bioconjugate py-macrodipa-PSMA, which was subsequently radiolabeled with large 132/135 La 3+ and small 47 Sc 3+ , revealing efficient and quantitative complex formation. The resulting radiocomplexes were injected into mice bearing both PSMA-expressing and PSMA-non-expressing tumor xenografts to determine their biodistribution patterns, revealing delivery of both 132/135 La 3+ and 47 Sc 3+ to PSMA+ tumor sites. However, partial radiometal dissociation was observed, suggesting that py-macrodipa-PSMA needs further structural optimization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗