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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 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Pre- and post-treatment image-based dosimetry in 90 Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit

Objective.To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy. Approach. In this study, five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme. Main results. TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy GBq -1 (2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 to 6.3 Gy GBq -1 and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose. Significance. Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Health Hazards of Exposures to Radioiodine

Iodine is a chemical element with atomic number 53. Iodine-127 is stable (non-radioactive) and commonly found in nature. Elemental iodine is a purple-colored solid at room temperature and pressure, but spontaneously sublimates (turns into vapor). Iodine is an essential element for life, and is required for proper functioning of the thyroid. Iodine is present in many foods, and is readily absorbed by the body and concentrated in the thyroid gland. A fraction of iodine ingested or inhaled is rapidly removed by the kidneys. The rest of the inhaled or ingested iodine is absorbed the by thyroid and retained for many months. Iodine has a biological half-life of approximately 120 days in health individuals. The biological half-life can be shorter in individuals with hyperthyroidism, and longer in individuals with hypothyroidism. Iodine has a number of radioactive isotopes, most of which have relatively short half-lives (days or weeks). Short half-life iodine isotopes are useful for a variety of medical applications, including imaging and cancer therapy. For example, Iodine-123 (half-life 13 hours) is commonly used for medical imaging of the thyroid, while iodine-131 (half-life 8 days) is used for suppressing thyroid function in individuals with hyperthyroidism or ablating (killing) thyroid cells to treat thyroid cancer. Iodine-125 (half-life 59 days) is produced in nuclear reactors, and has medical uses. Although iodine-125 can be used for thyroid imaging, Iodine-123 is more commonly used for that purpose because of its shorter half-life and higher-energy emissions. Iodine-125 is more commonly used for cancer treatment, and can be processed into small metal pellets (seeds) inserted directly into a tumor. Iodine-125 emits low-energy x-rays which can kill tumor cells and generally cannot escape the tumor, sparing other tissues. Medical iodine for imaging or treatment is typically administered orally in the form a pill or liquid solution. A typical adult thyroid scan using iodine-123 involves having the patient swallow between one and four 0.1 millicuries pills, with the exact dose dependent on the patient’s weight. This results in a whole-body committed effective dose of 80 – 320 mrem, and a thyroid equivalent dose of 1443 – 5772 mrem. Note that the whole-body effective dose relates to the overall cancer risk, while the larger equivalent dose to the thyroid only indicates that most of this risk is the result of exposure to the thyroid. These doses are considered safe, although the procedure is not recommended for pregnant or breastfeeding women. In contrast, the quantities of iodine-131 used for treatment of hyperthyroidism and thyroid cancers are much higher. For treatment of hyperthyroidism, 4 – 10 millicuries are administered, while for thyroid cancer the administration can range from 50 – 150 millicuries of I-131. In addition to medical exposures, large populations were exposed to radioiodine as result of the atomic bombings of Hiroshima and Nagasaki in Japan, and the Chernobyl nuclear accident. These populations have been carefully followed for many years to assess the effect of their radiation exposures on cancer risk. As a result, a great deal is known about the cancer risks associated with radioiodine exposure. Because iodine is concentrated in the thyroid, the principal risk of exposure to radioiodine is thyroid cancer. Children have the highest risk of thyroid cancer after exposure to radioactive iodine. According to a large study of Japanese atomic bomb survivors, an effective dose of one Sievert (100,000 mrem) has been observed to increase the risk of thyroid cancer by a factor of 9.5 in children aged zero to nine years old, by a factor of 3 in children aged 10 to 19 years old, and by barely detectable amounts in adults. Another way of quantifying the risk from radioiodine exposure is from risk coefficients, which provide the risk per unit intake of radionuclides in terms of both morbidity (any cancer) and mortality (death). Both morbidity (risk of cancer) and mortality (death) risks are shown in the table below. Note that because thyroid cancer is almost never fatal, the morbidity coefficients are much larger than the mortality coefficients.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2024

The safety of magnetic resonance imaging contrast agents

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum

Fetal alcohol spectrum disorders (FASD) caused by developmental ethanol exposure lead to cerebellar impairments, including motor problems, decreased cerebellar weight, and cell death. Alterations in the sole output of the cerebellar cortex, Purkinje cells, and central nervous system immune cells, microglia, have been reported in animal models of FASD. To determine how developmental ethanol exposure affects adult cerebellar microglia and Purkinje cells, we used a human third-trimester binge exposure model in which mice received ethanol or saline from postnatal (P) days 4–9. In adolescence, cerebellar cranial windows were implanted and mice were aged to young adulthood for examination of microglia and Purkinje cells in vivo with two-photon imaging or in fixed tissue. Ethanol had no effect on microglia density, morphology, dynamics, or injury response. However, Purkinje cell linear frequency was reduced by ethanol. Microglia–Purkinje cell interactions in the Purkinje Cell Layer were altered in females compared to males. Overall, developmental ethanol exposure had few effects on cerebellar microglia in young adulthood and Purkinje cells appeared to be more susceptible to its effects.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution

The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems-level understanding of molecular changes underlying the mechanisms leading to the histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we advance our metabolome-informed proteome imaging (MIPI) workflow to include lipidomic imaging, while also expanding the molecular coverage of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). The improved MIPI workflow advances biomedical investigations by leveraging state-of-the-art molecular imaging technologies. Lipidome imaging identifies molecular differences between two morphologically distinct compartments of a placental villous functional unit, syncytiotrophoblast (STB) and villous core. Next, our advanced metabolome imaging maps villous functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villous compartments. Complementary proteome imaging on these villous functional units reveals a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and villous core compartments. Integration across our advanced MIPI imaging modalities enables the reconstruction of active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villous compartments with micrometer-scale resolution.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Toward nanoscale molecular mass spectrometry imaging via physically constrained machine learning on co-registered multimodal data

Mass spectrometry imaging (MSI) plays a pivotal role in investigating the chemical nature of complex systems that underly our understanding in biology and medicine. Multiple fields of life science such as proteomics, lipidomics and metabolomics benefit from the ability to simultaneously identify molecules and pinpoint their distribution across a sample. However, achieving the necessary submicron spatial resolution to distinguish chemical differences between individual cells and generating intact molecular spectra is still a challenge with any single imaging approach. Here, we developed an approach that combines two MSI techniques, matrix-assisted laser desorption/ionization (MALDI) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), one with low spatial resolution but intact molecular spectra and the other with nanometer spatial resolution but fragmented molecular signatures, to predict molecular MSI spectra with submicron spatial resolution. The known relationships between the two MSI channels of information are enforced via a physically constrained machine-learning approach and directly incorporated in the data processing. We demonstrate the robustness of this method by generating intact molecular MALDI-type spectra and chemical maps at ToF-SIMS resolution when imaging mouse brain thin tissue sections. This approach can be readily adopted for other types of bioimaging where physical relationships between methods have to be considered to boost the confidence in the reconstruction product.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research

Widely used cone beam computed tomography (CBCT)-guided irradiators in preclinical radiation research are limited to localize soft tissue target because of low imaging contrast. Knowledge of target volume is a fundamental need for radiation therapy (RT). Without such information to guide radiation, normal tissue can be overirradiated, introducing experimental uncertainties. This led us to develop high-contrast quantitative bioluminescence tomography (QBLT) for guidance. The use of a 3-dimensional bioluminescence signal, related to cell viability, for preclinical radiation research is one step toward biology-guided RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Using AI Segmentation Models to Improve Foreign Body Detection and Triage from Ultrasound Images

Medical imaging can be a critical tool for triaging casualties in trauma situations. In remote or military medicine scenarios, triage is essential for identifying how to use limited resources or prioritize evacuation for the most serious cases. Ultrasound imaging, while portable and often available near the point of injury, can only be used for triage if images are properly acquired, interpreted, and objectively triage scored. Here, we detail how AI segmentation models can be used for improving image interpretation and objective triage evaluation for a medical application focused on foreign bodies embedded in tissues at variable distances from critical neurovascular features. Ultrasound images previously collected in a tissue phantom with or without neurovascular features were labeled with ground truth masks. These image sets were used to train two different segmentation AI frameworks: YOLOv7 and U-Net segmentation models. Overall, both approaches were successful in identifying shrapnel in the image set, with U-Net outperforming YOLOv7 for single-class segmentation. Both segmentation models were also evaluated with a more complex image set containing shrapnel, artery, vein, and nerve features. YOLOv7 obtained higher precision scores across multiple classes whereas U-Net achieved higher recall scores. Using each AI model, a triage distance metric was adapted to measure the proximity of shrapnel to the nearest neurovascular feature, with U-Net more closely mirroring the triage distances measured from ground truth labels. Overall, the segmentation AI models were successful in detecting shrapnel in ultrasound images and could allow for improved injury triage in emergency medicine scenarios.

47 OTHER INSTRUMENTATION↗
DOE OSTI2022

Transformative Technology for FLASH Radiation Therapy: A Snowmass 2021 White Paper

Conventional cancer therapies include surgery, radiation therapy, chemotherapy, and, more recently, immunotherapy. These modalities are often combined to improve the therapeutic index. The general concept of radiation therapy is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and high radiation beams that deliver radiation dose with high conformality, e.g., protons and ions. However, treatment and cure are still limited by normal tissue radiation toxicity, with many patients experiencing acute and long-term side effects. Recently, however, a fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. The dose delivery conditions are not yet fully characterized. Still, it is currently estimated that large doses of 10 Gy or more delivered in 200 ms or less produce normal tissue sparing effects yet effectively kill tumor cells. There is a great opportunity, but also many technical challenges, for the accelerator community to create the required dose rates with novel and compact accelerators to ensure the safe delivery of FLASH radiation beams.

43 PARTICLE ACCELERATORS↗
DOE OSTI2023

Transformative Technology for FLASH Radiation Therapy

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams.

43 PARTICLE ACCELERATORS↗
DOE OSTI2024

Toward Smart, Automated Junctional Tourniquets—AI Models to Interpret Vessel Occlusion at Physiological Pressure Points

Hemorrhage is the leading cause of preventable death in both civilian and military medicine. Junctional hemorrhages are especially difficult to manage since traditional tourniquet placement is often not possible. Ultrasound can be used to visualize and guide the caretaker to apply pressure at physiological pressure points to stop hemorrhage. However, this process is technically challenging, requiring the vessel to be properly positioned over rigid boney surfaces and applying sufficient pressure to maintain proper occlusion. As a first step toward automating this life-saving intervention, we demonstrate an artificial intelligence algorithm that classifies a vessel as patent or occluded, which can guide a user to apply the appropriate pressure required to stop flow. Neural network models were trained using images captured from a custom tissue-mimicking phantom and an ex vivo swine model of the inguinal region, as pressure was applied using an ultrasound probe with and without color Doppler overlays. Using these images, we developed an image classification algorithm suitable for the determination of patency or occlusion in an ultrasound image containing color Doppler overlay. Separate AI models for both test platforms were able to accurately detect occlusion status in test-image sets to more than 93% accuracy. In conclusion, this methodology can be utilized for guiding and monitoring proper vessel occlusion, which, when combined with automated actuation and other AI models, can allow for automated junctional tourniquet application.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Engineered Glucose Oxidase‐Carbon Nanotube Conjugates for Tissue‐Translatable Glucose Nanosensors

Abstract Continuous and non‐invasive glucose monitoring and imaging is important for disease diagnosis, treatment, and management. However, glucose monitoring remains a technical challenge owing to the dearth of tissue‐transparent glucose sensors. In this study, we present the development of near‐infrared fluorescent single‐walled carbon nanotube (SWCNT) based nanosensors directly functionalized with glucose oxidase (GOx) capable of immediate and reversible glucose imaging in biological fluids and tissues. We prepared GOx‐SWCNT nanosensors by facile sonication of SWCNT with GOx in a manner that—surprisingly—does not compromise the ability of GOx to detect glucose. Importantly, we find by using denatured GOx that the fluorescence modulation of GOx‐SWCNT is not associated with the catalytic oxidation of glucose but rather triggered by glucose‐GOx binding. Leveraging the unique response mechanism of GOx‐SWCNT nanosensors, we developed catalytically inactive apo‐GOx‐SWCNT that enables both sensitive and reversible glucose imaging, exhibiting a ΔF/F 0 of up to 40 % within 1 s of exposure to glucose without consuming the glucose analyte. We finally demonstrate the potential applicability of apo‐GOx‐SWCNT in biomedical applications by glucose quantification in human plasma and glucose imaging in mouse brain slices.

Chemistry↗
DOE OSTI2023

Plasmonic nanorod probes’ journey inside plant cells for in vivo SERS sensing and multimodal imaging

Nanoparticle-based platforms are gaining strong interest in plant biology and bioenergy research to monitor and control biological processes in whole plants. However, in vivo monitoring of biomolecules using nanoparticles inside plant cells remains challenging due to the impenetrability of the plant cell wall to nanoparticles beyond the exclusion limits (5-20 nm). To overcome this physical barrier, we have designed unique bimetallic silver-coated gold nanorods (AuNR@Ag) capable of entering plant cells, while conserving key plasmonic properties in the near-infrared (NIR). To demonstrate cellular internalization and tracking of the nanorods inside plant tissue, we used a comprehensive multimodal imaging approach that included transmission electron microscopy (TEM), confocal fluorescence microscopy, two-photon luminescence (TPL), X-ray fluorescence microscopy (XRF), and photoacoustics imaging (PAI). We successfully acquired SERS signals of nanorods in vivo inside plant cells of tobacco leaves. On the same leaf samples, we applied orthogonal imaging methods, TPL and PAI techniques for in vivo imaging of the nanorods. This study first demonstrates the intracellular internalization of AuNR@Ag inside whole plant systems for in vivo SERS analysis in tobacco cells. This work demonstrates the potential of this nanoplatform as a new nanotool for intracellular in vivo biosensing for plant biology.

Cupil-Garcia, Vanessa↗
DOE OSTI2021

Bi-terminal pegylated integrin-binding peptides and methods of use thereof

The present invention provides bi-terminal PEGylated peptide conjugates that target an integrin such as αvβ6 integrin. In particular embodiments, the peptide conjugates of the present invention further comprise a biological agent such as an imaging agent or a therapeutic agent, e.g., covalently attached to one of the PEG moieties. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue and for treating integrin-mediated diseases and disorders such as cancer, inflammatory diseases, autoimmune diseases, chronic fibrosis, chronic obstructive pulmonary disease (COPD), lung emphysema, and chronic wounding skin disease. Compositions and kits containing the peptide conjugates of the present invention find utility in a wide range of applications including, e.g., in vivo imaging and immunotherapy.

Hausner, Sven H.↗
DOE OSTI2022

Bi-terminal pegylated integrin-binding peptides and methods of use thereof

The present invention provides bi-terminal PEGylated peptide conjugates that target an integrin such as αvβ6 integrin. In particular embodiments, the peptide conjugates of the present invention further comprise a biological agent such as an imaging agent or a therapeutic agent, e.g., covalently attached to one of the PEG moieties. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue and for treating integrin-mediated diseases and disorders such as cancer, inflammatory diseases, autoimmune diseases, chronic fibrosis, chronic obstructive pulmonary disease (COPD), lung emphysema, and chronic wounding skin disease. Compositions and kits containing the peptide conjugates of the present invention find utility in a wide range of applications including, e.g., in vivo imaging and immunotherapy.

Hausner, Sven H.↗
DOE OSTI2022

Computer-aided Veress needle guidance using endoscopic optical coherence tomography and convolutional neural networks

During laparoscopic surgery, the Veress needle is commonly used in pneumoperitoneum establishment. Precise placement of the Veress needle is still a challenge for the surgeon. In this study, a computer-aided endoscopic optical coherence tomography (OCT) system was developed to effectively and safely guide Veress needle insertion. This endoscopic system was tested by imaging subcutaneous fat, muscle, abdominal space, and the small intestine from swine samples to simulate the surgical process, including the situation with small intestine injury. Each tissue layer was visualized in OCT images with unique features and subsequently used to develop a system for automatic localization of the Veress needle tip by identifying tissue layers (or spaces) and estimating the needle-to-tissue distance. We used convolutional neural networks (CNNs) in automatic tissue classification and distance estimation. In conclusion, the average testing accuracy in tissue classification was 98.53 ± 0.39%, and the average testing relative error in distance estimation reached 4.42 ± 0.56% (36.09 ± 4.92 μm).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Spatial metabolomics and lipidomics in kidney disease

Kidney disease is a global health issue that affects over 850 million people, and early detection is key to preventing severe disease and complications. Kidney diseases are associated with complex dysregulation of lipid metabolism. Spatial metabolomics through mass spectrometry imaging (MSI) enables spatial mapping of the lipids in tissue and includes a variety of techniques that can be used to image lipids. In the kidney MSI studies often seek to resolve individual functional tissue units such as glomeruli and proximal tubules. Several different MSI techniques such as matrix-assisted laser desorption/ionization and desorption electrospray ionization have been used to characterize lipids and small molecules in chronic kidney disease, acute kidney injury, genetic kidney disease, and cancer. In this review we provide several examples of how spatial metabolomics data can provide critical information concerning localization of changes in disease states. Additionally, when combined with pathology, measurements, transcriptomics, or proteomics, the metabolomic changes can illuminate underlying mechanisms and provide new clinical insights.

59 BASIC BIOLOGICAL SCIENCES↗