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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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7 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

A 1D–0D–3D coupled model for simulating blood flow and transport processes in breast tissue

In this work, we present mixed dimensional models for simulating blood flow and transport processes in breast tissue and the vascular tree supplying it. These processes are considered, to start from the aortic inlet to the capillaries and tissue of the breast. Large variations in biophysical properties and flow conditions exist in this system necessitating the use of different flow models for different geometries and flow regimes. In total, we consider four different model types. First, a system of 1D nonlinear hyperbolic partial differential equations (PDEs) is considered to simulate blood flow in larger arteries with highly elastic vessel walls. Second, we assign 1D linearized hyperbolic PDEs to model the smaller arteries with stiffer vessel walls. The third model type consists of ODE systems (0D models). It is used to model the arterioles and peripheral circulation. Finally, homogenized 3D porous media models are considered to simulate flow and transport in capillaries and tissue within the breast volume. Sink terms are used to account for the influence of the venous and lymphatic systems. Combining the four model types, we obtain two different 1D–0D–3D coupled models for simulating blood flow and transport processes: The first model results in a fully coupled 1D–0D–3D model covering the complete path from the aorta to the breast combining a generic arterial network with a patient specific breast network and geometry. The second model is a reduced one based on the separation of the generic and patient specific parts. The information from a calibrated fully coupled model is used as inflow condition for the patient specific sub-model allowing a significant computational cost reduction. Several numerical experiments are conducted to calibrate the generic model parameters and to demonstrate realistic flow simulations compared to existing data on blood flow in the human breast and vascular system. Moreover, we use two different breast vasculature and tissue data sets to illustrate the robustness of our reduced sub-model approach.

multiscale blood flow models↗
DOE OSTI2024

A MPET 2 -mPBPK model for subcutaneous injection of biotherapeutics with different molecular weights: From local scale to whole-body scale

Subcutaneous injection of biotherapeutics has attracted considerable attention in the pharmaceutical industry. However, there is limited understanding of the mechanisms underlying the absorption of drugs with different molecular weights and the delivery of drugs from the injection site to the targeted tissue. Here, we propose the MPET 2 -mPBPK model to address this issue. This multiscale model couples the MPET 2 model, which describes subcutaneous injection at the local tissue scale from a biomechanical view, with a post-injection absorption model at injection site and a minimal physiologically-based pharmacokinetic (mPBPK) model at whole-body scale. Utilizing the principles of tissue biomechanics and fluid dynamics, the local MPET 2 model provides solutions that account for tissue deformation and drug absorption in local blood vessels and initial lymphatic vessels during injection. Additionally, we introduce a model accounting for the molecular weight effect on the absorption by blood vessels, and a nonlinear model accounting for the absorption in lymphatic vessels. The post-injection model predicts drug absorption in local blood vessels and initial lymphatic vessels, which are integrated into the whole-body mPBPK model to describe the pharmacokinetic behaviors of the absorbed drug in the circulatory and lymphatic system. We establish a numerical model which links the biomechanical process of subcutaneous injection at local tissue scale and the pharmacokinetic behaviors of injected biotherapeutics at whole-body scale. With the help of the model, we propose an explicit relationship between the reflection coefficient and the molecular weight and predict the bioavalibility of biotherapeutics with varying molecular weights via subcutaneous injection. The considered drug absorption mechanisms enable us to study the differences in local drug absorption and whole-body drug distribution with varying molecular weights. This model enhances the understanding of drug absorption mechanisms and transport routes in the circulatory system for drugs of different molecular weights, and holds the potential to facilitate the application of computational modeling to drug formulation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Go with the flow: modeling unique biological flows in engineered in vitro platforms

Interest in recapitulating in vivo phenomena in vitro using organ-on-a-chip technology has grown rapidly and with it, attention to the types of fluid flow experienced in the body has followed suit. These platforms offer distinct advantages over in vivo models with regards to human relevance, cost, and control of inputs (e.g., controlled manipulation of biomechanical cues from fluid perfusion). Given the critical role biophysical forces play in several tissues and organs, it is therefore imperative that engineered in vitro platforms capture the complex, unique flow profiles experienced in the body that are intimately tied with organ function. In this review, we outline the complex and unique flow regimes experienced by three different organ systems: blood vasculature, lymphatic vasculature, and the intestinal system. Here, we highlight current state-of-the-art platforms that strive to replicate physiological flows within engineered tissues while introducing potential limitations in current approaches.

42 ENGINEERING↗
DOE OSTI2024

Mortality of older construction and craft workers employed at Department of Energy (DOE) nuclear sites: Follow‐up through 2021

Background To determine if construction and trades workers formerly employed at US Department of Energy (DOE) nuclear weapons sites are at significant risk for occupational diseases, we studied the mortality experience of participants in the Building Trades National Medical Screening Program (BTMed). Methods The cohort included 26,922 participants enrolled between 1998 and 2021 and 8367 deaths. Standardized mortality ratios were calculated based on US death rates. Cox models compared construction workers (n = 22,747; 7487 deaths) to two nonconstruction subpopulations: administrative, scientific and security workers (n = 1894; 330 deaths), and all other nonconstruction workers (n = 2218; 550 deaths). Results Mortality was elevated for all causes, all cancers, cancers of the trachea, bronchus, lung, kidneys, and lymphatic and hematopoietic system, mesothelioma, chronic obstructive pulmonary disease (COPD), asbestosis, transportation injuries, and other injuries, particularly accidental poisonings. There were 167 deaths from coronavirus disease 2019 (COVID-19), which was lower than expected using US death rates. Overall cause-specific mortality was significantly higher among construction workers than for internal comparison groups. Conclusions Construction workers employed at DOE sites have a significantly increased risk for occupational illnesses. Apart from COVID-19 deaths, this update: (1) found that mortality among construction workers is significantly elevated compared to the US population and significantly higher than in the internal comparison populations, and (2) confirmed excess risk for these workers for first employment after 1990. Cancer mortality risks are similar to the cancers identified for DOE compensation from radiation exposures. In conclusion, the high lung cancer risk supports the value of early lung cancer detection. Continued medical surveillance is important.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2023

Modeling immunity in microphysiological systems

There is a need for better predictive models of the human immune system to evaluate safety and efficacy of immunomodulatory drugs and biologics for successful product development and regulatory approvals. Current in vitro models, which are often tested in two-dimensional (2D) tissue culture polystyrene, and preclinical animal models fail to fully recapitulate the function and physiology of the human immune system. Microphysiological systems (MPSs) that can model key microenvironment cues of the human immune system, as well as of specific organs and tissues, may be able to recapitulate specific features of the in vivo inflammatory response. This minireview provides an overview of MPS for modeling lymphatic tissues, immunity at tissue interfaces, inflammatory diseases, and the inflammatory tumor microenvironment in vitro and ex vivo. Broadly, these systems have utility in modeling how certain immunotherapies function in vivo, how dysfunctional immune responses can propagate diseases, and how our immune system can combat pathogens.

Research & Experimental Medicine↗
DOE OSTI2020

Evaluation of camera-based freehand SPECT in preoperative sentinel lymph node mapping for melanoma patients

Assessment of lymphatic status via sentinel lymph node (SLN) biopsy is an integral and crucial part of melanoma surgical oncology. The most common technique for sentinel node mapping is preoperative planar scintigraphy of an injected gamma-emitting lymphatic tracer followed by intraoperative node localization using a non-imaging gamma probe with auditory feedback. In recent years, intraoperative visualization of SLNs in 3D has become possible by coupling the probe to an external system capable of tracking its location and orientation as it is read out, thereby enabling computation of the 3D distribution of the tracer (freehand SPECT). In this project, the non-imaging probe of the fhSPECT system was replaced by a unique handheld gamma camera containing an array of sodium iodide crystals optically coupled to an array of silicon photomultipliers (SiPMs). A feasibility study was performed in which preoperative SLN mapping was performed using camera fhSPECT and the number of detected nodes was compared to that visualized by lymphoscintigraphy, probe fhSPECT, and to the number ultimately excised under non-imaging probe guidance. Among five subjects, SLNs were detected in nine lymphatic basins, with one to five SLNs detected per basin. A basin-by-basin comparison showed that the number of SLNs detected using camera fhSPECT exceeded that using lymphoscintigraphy and probe fhSPECT in seven of nine basins and five of five basins, respectively. (Probe fhSPECT scans were not performed for four basins.) It exceeded the number excised under non-imaging probe guidance for seven of nine basins and equaled the number excised for the other two basins. Freehand SPECT using a prototype SiPM-based gamma camera demonstrates high sensitivity for detection of SLNs in a preoperative setting. Camera fhSPECT is a potential means for efficiently obtaining real-time 3D activity distribution maps in applications such as image-guided percutaneous biopsy, and surgical SLN biopsy or radioguided tumor excision.

60 APPLIED LIFE SCIENCES↗