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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 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
NASA NTRS2013

NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential effectiveness of radiation mitigator's. The NSRM- 2014 approaches to model radiation quality dependent lethality and NTE's will be described. CNS effects include both early changes that may occur during long space missions and late effects such as Alzheimer's disease (AD). AD effects 50% of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages and the small number of low LET epidemiology studies undertaken have not identified an association with low dose radiation. However experimental studies in mice suggest GCR may lead to early onset AD. We discuss modeling approaches to consider mechanisms whereby radiation would lead to earlier onset of occurrence of AD. Biomarkers of AD include amyloid beta (A(Beta)) plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyperphosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dentritic spine loss, and neuronal cell loss through apoptosis. Radiation may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuroinflammation. Cell types to be considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3(Beta) (GSK3(Beta)) and neuroinflammation, and considered multi-scale modeling approaches to develop computer simulations of cell interactions and their relationships to A(Beta) plaques and NFTs. Comparison of model results to experimental data for the age specific development of A(Beta) plaques in transgenic mice will be discussed.

Cucinotta, Francis A.↗
NASA NTRS2014

Recent Weather Extremes and Impacts on Agricultural Production and Vector-Borne Disease Outbreak Patterns

We document significant worldwide weather anomalies that affected agriculture and vector-borne disease outbreaks during the 2010-2012 period. We utilized 2000-2012 vegetation index and land surface temperature data from NASA's satellite-based Moderate Resolution Imaging Spectroradiometer (MODIS) to map the magnitude and extent of these anomalies for diverse regions including the continental United States, Russia, East Africa, Southern Africa, and Australia. We demonstrate that shifts in temperature and/or precipitation have significant impacts on vegetation patterns with attendant consequences for agriculture and public health. Weather extremes resulted in excessive rainfall and flooding as well as severe drought, which caused,10 to 80% variation in major agricultural commodity production (including wheat, corn, cotton, sorghum) and created exceptional conditions for extensive mosquito-borne disease outbreaks of dengue, Rift Valley fever, Murray Valley encephalitis, and West Nile virus disease. Analysis of MODIS data provided a standardized method for quantifying the extreme weather anomalies observed during this period. Assessments of land surface conditions from satellite-based systems such as MODIS can be a valuable tool in national, regional, and global weather impact determinations.

Weather↗
NASA NTRS2018

Cardiovascular Disease Outcomes Among the NASA Astronaut Corps

BACKGROUND: Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in spaceflight activities are associated with changes in the cardiovascular system such as decreased carotid artery distensibility and decreased ventricular mass which may lead to an increased risk of cardiovascular disease. Additionally, astronauts who travel into space multiple times or for longer durations may be at an increased risk across their lifespan. To that end, the purpose of this study was to determine the incidence of common cardiovascular disease (CVD) outcomes among the NASA astronaut corps during their active career and through retirement. METHODS: Cardiovascular disease outcomes were defined as reports of any of the following: myocardial infarction (MI), revascularization procedures (coronary artery bypass graft surgery [CABG] or percutaneous coronary intervention [PCI]), hypertension, stroke or transient ischemic attack [TIA], heart failure, or total CVD (as defined by the AHA - combined outcome of MI, Angina Pectoris, heart failure, stroke, and hypertension). Each outcome was identified individually from review of NASA's Electronic Medical Record (EMR), EKG reports, and death certificates using ICD-9 codes as well as string searches of physician notes of astronaut exams that occurred between 1959 and 2016. RESULTS: Of 338 NASA astronauts selected as of 2016, 9 reported an MI, 12 reported a revascularization procedure, (7 PCI and 5 CABG), 4 reported Angina (without MI), 5 reported heart failure, 9 reported stroke/TIA, and 96 reported hypertension. Total CVD was reported in 105 astronauts. No astronaut who had an MI or revascularization procedure flew a spaceflight mission following the event. All MI, revascularization, and stroke events occurred in male astronauts. When reviewing astronaut ECG reports, abnormal ECG reports were found in only 8% of records (n=430) and mainly among retired astronauts (82%), with marked sinus bradycardia being the reason for the abnormal classification.

Charvat, Jacqueline M.↗
NASA NTRSDate not supplied

Outcomes of a NASA Human Research Program’s (HRP) Space Radiation Element-sponsored Mini-Technical Interchange Meeting/workshop on Cardiovascular Disease Risk from Space Radiation

The NASA HRP’s Space Radiation Element funds research to characterize and mitigate adverse health outcomes from space radiation including cardiovascular risks to astronauts to enable deep space exploration and sustained human presence in space. Non-cancer effects such as damage to the cardiovascular system have been observed at clinically relevant high doses of ionizing radiation. However, an association between lower doses and risk of cardiovascular disease (CVD) remains somewhat controversial, especially in relation to the existence of low dose thresholds, radiation quality, and dose-rate effects, as well as gaps in characterizing the mechanisms and major pathways of disease. To facilitate, accelerate, and incubate new ideas to characterize and mitigate this risk, the Element is planning to organize a series of miniature technical interchange meetings (Tiny-TIMs) to provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on presented results, limitations of current approaches, incorporating better experimental strategies, model systems, etc. The initial Tiny-TIM held during the NASA HRP Investigators’ Workshop earlier this year – Upping the ante on characterizing and mitigating cardiovascular disease risk from space radiation exposure – aimed to stimulate discussion on the current state of scientific knowledge of CVD risk from space-like radiation exposure. The Tiny-TIM consisted of two 90-minute sessions; the first session concentrated on current knowledge of CVD risk from space radiation and the second session focused on innovative ideas, newer approaches, and techniques to accelerate research. The second session was followed by an open spirited discussion amongst peers on the current issues impeding the characterization of CVD risk from space radiation. The Element facilitated the discussion using a set of pressing open questions/gaps in knowledge that need to be addressed by the scientific community. The outcomes of the Tiny-TIM will be presented along with a plan of proposed future workshops and other initiatives of the Space Radiation Element.

Janapriya Saha↗
NASA NTRS2025

Influence of Microgravity on Bacterial Pathogen Virulence and Immune Cell Function—Relevance for Infectious Disease Risk During Spaceflight

Spaceflight has measurable impacts on astronaut immune profiles as well as the virulence patterns of bacterial pathogens. Data with respect to human immunity indicate diminished T and NK cell function, altered cytokine profiles, persistent inflammation, and latent herpesvirus reactivation. Furthermore, evaluation of International Space Station (ISS) crewmembers gives evidence of compromised immunity, including atypical allergy, infectious disease, and dermatitis. Data with respect to certain human bacterial pathogens suggest modified virulence that may be enhanced. It is therefore critical to examine this interaction of immune dysregulation and increased microbial virulence and whether it might synergistically increase the risk of infectious disease to crew members. The goal of this study is to use modeled microgravity to study the impact of medically significant ISS bacteria that may have altered virulence on the immune response of the host. This study consists of two primary aims to assess this relationship. First, immune cells will be collected from healthy test subjects and cultured in static or in modeled microgravity conditions together with either control pathogens or with microgravity conditioned pathogens that were grown in bioreactors. Second, immune cells will be collected from astronauts before, during, and after flight and co-cultured with the control or the microgravity conditioned bacteria. Three pathogens were selected for this investigation: Pseudomonas aeruginosa , Salmonella enterica serovar Enteritidis and Burkholderia cepacia . Previously, the optimal cell to bacteria ratios that produce the greatest immune cell responses have been derived for these three bacteria. Cellular activation, as determined by the induction of cell surface activation markers and cytokine profiles, will be measured. Interactions between cells and bacteria will be assessed using fluorescent and electron microscopy techniques. This study will provide critical information to help understand how microgravity alters microbial virulence and the associated infectious disease risk to crewmembers during spaceflight missions. Over the past year, the Immunology and Microbiology laboratories at NASA Johnson Space Center have collaborated to process the astronaut subject samples to complete the last year of the flight portion of this study. This included the completion of four astronaut subjects full mission sampling sets. Sample processing included innate and adaptive cell flow cytometry as well as analysis of cytokine concentrations in the supernatant. The ground control segment of the study will take place during FY25 which involves parallel infections run under static and clinostat conditions. The acquired data sets over this 3-year study are now being analyzed to provide a comprehensive set of results and conclusions that will contribute to a more effective risk assessment for astronauts during spaceflight regarding this host-pathogen context.

Immunology↗
DOE OSTI2013

Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

data analytics↗
DOE OSTI2023

Nerve stimulation for treatment of diseases and disorders

Methods are disclosed for treating a subject having a disease or disorder comprising stimulating a nerve of the subject with a corrective stimulus pattern derived from a disease-specific, condition-specific, endogenous mediator-specific or pharmacologic agent-specific neurogram in an amount and manner effective to treat the disease or disorder.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Methods for promoting myelination and for treating demyelinating diseases

This invention provides novel methods for treating or ameliorating symptoms of demyelinating diseases such as multiple sclerosis. The methods involve administering to subjects in need of treatment a pharmaceutical composition that contains a therapeutically effective amount of taurine and also a compound that induces oligodendrocyte precursor cell (OPC) differentiation (e.g., T3, benztropine, clemastine or miconazole). Some of the methods additionally involve administration to the subject a known agent for treating demyelinating diseases (e.g., SIP receptor agonists) or a known disease modifying drug. The invention also provides methods for increasing myelination and methods for promoting OPC differentiation into oligodendrocytes. These methods entail contacting a population of OPCs with a combination of taurine and a known OPC differentiation-inducing agent such as T3, clemastine, benztropine or miconazole.

Lairson, Luke↗
DOE OSTI2024

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer’s disease: A putative biomarker of amyloid-induced vascular damage

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance. Additionally, we sought to replicate FLT1 interactions in the brain. The results showed that higher levels of FLT1 in CSF and post-mortem brain tissue related to increased tau, particularly among amyloid positive individuals. These analyses help clarify the potential utility of FLT1 as a biomarker among individuals with evidence of brain amyloidosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Parkinson's disease-associated mutations in the GTPase domain of LRRK2 impair its nucleotide-dependent conformational dynamics

Mutation in Leucine Rich Repeat Kinase 2 (LRRK2) is a common cause of familial Parkinson's disease (PD). Recently, we showed that a disease-associated mutation R1441H rendered the GTPase domain of LRRK2 catalytically less active and thereby trapping it in a more persistently "on" conformation. However, the mechanism involved and characteristics of this "on" conformation remained unknown. Here, we report that the ROC domain of LRRK2 exists in a dynamic dimermonomer equilibrium that is oppositely driven by GDP and GTP binding. We also observed that the diseaseassociated mutations at residue 1441 impair this dynamic and shift the conformation of ROC to a GTPbound- like monomeric conformation. Moreover, we show that residue arginine 1441 is critical for regulating the conformational dynamics of ROC. In summary, our results reveal that the PD-associated substitutions at Arg-1441 of LRRK2 alter monomerdimer dynamics and thereby trap its GTPase domain in an activated state.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Modeling Alzheimer’s Disease Progression with Fused Laplacian Sparse Group Lasso

Alzheimer’s disease (AD), the most common type of dementia, not only imposes a huge financial burden on the health care system, but also a psychological and emotional burden on patients and their families. There is furthermore an urgent need to infer trajectories of cognitive performance over time and identify biomarkers predictive of the progression. Here, we introduce the multi-task learning with fused Laplacian sparse group lasso model, which can identify biomarkers closely related to cognitive measures due to its sparsity-inducing property, and model the disease progression with a general weighted (undirected) dependency graphs among the tasks. An efficient alternative directions method of multipliers based optimization algorithm is derived to solve the proposed non-smooth objective formulation. The effectiveness of the presented model is demonstrated by its superior prediction performance over multiple state-of-the-art methods and accurate identification of compact sets of cognition-relevant imaging biomarkers that are consistent with prior medical studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

Prion agents occur in strains that are encoded by the structure of the misfolded prion protein (PrP Sc ). Prion strains can influence disease phenotype and the potential for interspecies transmission. Little is known about the potential transmission of prions between sheep and deer. Previously, the classical US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to test the susceptibility of sheep to challenge with the scrapie agent after passage through white-tailed deer (WTD scrapie). Lambs of various prion protein genotypes were oronasally challenged with WTD scrapie. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Enzyme immunoassay, western blot, and immunohistochemistry demonstrated PrP Sc in 4 of 10 sheep with the fastest incubation occurring in VRQ/VRQ sheep, which contrasts the original No.13-7 inoculum with a faster incubation in ARQ/ARQ sheep. Shorter incubation periods in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer was suggestive of a phenotype change, so comparisons were made in ovinized mice and with sheep with known strains of classical sheep scrapie: No. 13–7 and x-124 (that has a more rapid incubation in VRQ/VRQ sheep). After mouse bioassay, the WTD scrapie and x-124 isolates have similar incubation periods and PrP Sc conformational stability that are markedly different than the original No. 13–7 inoculum. Furthermore, brain tissues of sheep with WTD scrapie and x-124 scrapie have similar patterns of immunoreactivity that are distinct from sheep with No. 13–7 scrapie. Multiple lines of evidence suggest a phenotype switch when No. 13–7 scrapie prions are passaged through deer. This represents one example of interspecies transmission of prions resulting in the emergence or selection of new strain properties that could confound disease eradication and control efforts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Assessment of a reconfiguration of the InterSpread Plus US national FMD model as a potential tool to analyze a foot-and-mouth disease outbreak on a single large cattle feedlot in the United States

An incursion of foot-and-mouth disease (FMD) into the United States remains a concern of high importance and would have devastating socioeconomic impacts to the livestock and associated industries. This highly transmissible and infectious disease poses continual risk for introduction into the United States (US), due to the legal and illegal global movement of people, animals, and animal products. While stamping out has been shown to effectively control FMD, depopulation of large cattle feedlots (>50,000 head) presents a number of challenges for responders due to the resources required to depopulate and dispose of large numbers of animals in a timely and effective manner. However, evaluating alternative strategies for FMD control on large feedlots requires a detailed within-farm modeling approach, which can account for the unique structure of these operations. To address this, we developed a single feedlot, within-farm spread model using a novel configuration within the InterSpread Plus (ISP) framework. As proof of concept we designed six scenarios: (i) depopulation - the complete depopulation of the feedlot, (ii) burn-through – a managed “burn-through” where the virus is allowed to spread through the feedlot and only movement restriction and biosecurity are implemented, (iii) firebreak-NV – targeted depopulation of infected pens and adjacent pens without vaccination; (iv) firebreak - targeted depopulation of infected pens and adjacent pens with vaccination of remaining pens; (v) harvest-NV - selective harvest of pens where a 100% movement restriction is applied for 28-30 days, then pens are set for selection to be sent to slaughter, while allowing a controlled “burn-through” without vaccination; and (vi) harvest - selective harvest of pens with vaccination. Overall, the burn-through scenario (ii) had the shortest epidemic duration (31d (30, 33)) median (25th, 75th percentiles), while the firebreak scenario (iv) had the longest (47d (38,55)). Additionally, we found that scenarios implementing depopulation delayed the peak day of infection and reduced the total number of pens infected compared to non-depopulation scenarios.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn’s Disease. Methods: 18 patients with mild/moderate CD (PCDAI 15–45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Brain phosphoproteomic analysis identifies diabetes‐related substrates in Alzheimer's disease pathology in older adults

INTRODUCTION: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored. METHODS: We performed tandem mass tag–based phosphoproteome profiling in post mortem human brain prefrontal cortex samples from 191 deceased older adults with and without diabetes and pathologic AD. RESULTS: Among 7874 quantified phosphosites, microtubule-associated protein tau (MAPT) phosphorylated at T529 and T534 (isoform 8 T212 and T217) were more abundant in AD and showed differential associations with diabetes. Network analysis of co-abundance patterns uncovered synergistic interactions between AD and diabetes, with one module exhibiting higher MAPT phosphorylation (15 MAPT phosphosites) and another displaying lower MAP1B phosphorylation (22 MAP1B phosphosites). DISCUSSION: This study offers phosphoproteomics insights into AD in diabetes, shedding light on mechanisms that can inform the development of therapeutics for dementia. Highlights: The risk of Alzheimer's disease (AD) dementia is increased among older adults living with diabetes. The patterns of AD-related phosphoprotein in the human brain in older adults are differential among older adults living with diabetes. Microtubule-associated protein tau phosphorylated at T529 and T534 (isoform 8 T212 and T217) showed differential associations with diabetes. Phosphosite co-abundance networks of synergistic interactions between AD and diabetes were identified.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Phenotype-driven approaches to enhance variant prioritization and diagnosis of rare disease

Rare disease diagnostics and disease gene discovery have been revolutionized by whole-exome and genome sequencing but identifying the causative variant(s) from the millions in each individual remains challenging. The use of deep phenotyping of patients and reference genotype-phenotype knowledge, alongside variant data such as allele frequency, segregation, and predicted pathogenicity, has proved an effective strategy to tackle this issue. Here we review the numerous tools that have been developed to automate this approach and demonstrate the power of such an approach on several thousand diagnosed cases from the 100,000 Genomes Project. Finally, we discuss the challenges that need to be overcome if we are going to improve detection rates and help the majority of patients that still remain without a molecular diagnosis after state-of-the-art genomic interpretation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Magnetic resonance elastography SE-EPI vs GRE sequences at 3T in a pediatric population with liver disease

Purpose: The goal of our study is to compare hepatic stiffness measures using gradient-recalled echo (GRE) versus spin-echo echo planar imaging (SE-EPI)-based MR Elastography (MRE) at 3T used to measure hepatic stiffness in a patients with suspected liver diseases. Materials and methods: This retrospective study included 52 patients with liver disease who underwent a 3T MRE exam including both an investigational SE-EPI-based technique and a product GRE-based technique. Regions of interest (ROI) were placed on the elastograms to measure elastography-derived liver stiffness as well as the area included within the ROIs. The mean liver stiffness values and area of ROIs were compared. Results: The mean liver stiffness was 3.72 kilopascal (kPa) ± 1.29 using GRE MRE and 3.78 kPa ± 1.13 using SE-EPI MRE. Measurement of liver stiffness showed excellent agreement between the two pulse sequences with a mean bias of − 0.1 kPa (range − 1.8 to 1.7 kPa) between sequences. The mean measurable ROI area was higher with SE-EPI (313.8 cm{sup 2} ± 213.8) than with the GRE technique (208.6 cm{sup 2} ± 114.8), and the difference was statistically significant (P < 0.05). Conclusions: Our data shows excellent agreement of measured liver stiffness between GRE and SE-EPI-based sequences at 3T. Our results show the advantage of a SE-EPI MRE sequence in terms of image quality, ROI size and acquisition time with equivalent liver stiffness measurements as compared to GRE-MRE sequence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗