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At least 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology

Abstract The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl− are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood–brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

Biochemistry & Molecular Biology↗
DOE OSTI2021

Brain Connectivity Workshop Series Report

The National Institutes of Health (NIH) BRAIN Initiative aims to accelerate development and application of technologies that show how individual brain cells in complex neural circuits interact at the speed of thought and action. Complete wiring diagrams of the mammalian brain will revolutionize the capabilities of researchers to formulate and test models of how activity within brain circuits drives coordinated function and behavior. A top priority for the BRAIN Initiative, motivated by the strategic guidance of the BRAIN 2.0 Working Group report, is to muster the resources and foster the collaborations needed to generate these wiring diagrams at the level of long-range projections (“projectomes”) and synapses (“connectomes”) in whole mammalian brains, including those from rodents, humans, and other large-brained mammals. Achieving the scale and resolution necessary to characterize and use these projectomes and connectomes will not only push the boundaries of current imaging and computational capabilities to generate faster, cheaper, and more scalable technologies, but also drive broad innovation in data science, artificial intelligence, and machine learning.

42 ENGINEERING↗
NASA NTRS2003

Application of a data-mining method based on Bayesian networks to lesion-deficit analysis

Although lesion-deficit analysis (LDA) has provided extensive information about structure-function associations in the human brain, LDA has suffered from the difficulties inherent to the analysis of spatial data, i.e., there are many more variables than subjects, and data may be difficult to model using standard distributions, such as the normal distribution. We herein describe a Bayesian method for LDA; this method is based on data-mining techniques that employ Bayesian networks to represent structure-function associations. These methods are computationally tractable, and can represent complex, nonlinear structure-function associations. When applied to the evaluation of data obtained from a study of the psychiatric sequelae of traumatic brain injury in children, this method generates a Bayesian network that demonstrates complex, nonlinear associations among lesions in the left caudate, right globus pallidus, right side of the corpus callosum, right caudate, and left thalamus, and subsequent development of attention-deficit hyperactivity disorder, confirming and extending our previous statistical analysis of these data. Furthermore, analysis of simulated data indicates that methods based on Bayesian networks may be more sensitive and specific for detecting associations among categorical variables than methods based on chi-square and Fisher exact statistics.

NASA Discipline Neuroscience↗
DOE OSTI2024

Untargeted Spatial Metabolomics and Spatial Proteomics on the Same Tissue Section

An increasing number of spatial multiomic workflows have been recently developed. Some of these approaches have leveraged initial mass spectrometry imaging (MSI)-based spatial metabolomics to inform region of interest (ROI) selection for downstream spatial proteomics. However, these workflows have been limited by varied substrate requirements between modalities or have required analyzing serial sections (i.e., one section per modality). To mitigate these issues, we present a novel multiomic workflow that uses desorption electrospray ionization (DESI)-MSI to identify representative spatial metabolite patterns on-tissue prior to spatial proteomic analyses on the same tissue section. Further, this workflow is demonstrated here with a model mammalian tissue (coronal rat brain section) mounted on a polyethylene naphthalate-membrane slide. Initial DESI-MSI resulted in 160 annotations (SwissLipids) within to the METASPACE platform (≤20% false discovery rate). A segmentation map from the annotated ion images informed downstream ROI selection for spatial proteomics characterization from the same sample. The unspecific substrate requirements and minimal sample disruption inherent to DESI-MSI allowed for an optimized, downstream spatial proteomics assay, resulting in 3888 ± 240 to 4717 ± 48 proteins being confidently directed per ROI (200 µm x 200 µm). Finally, we demonstrate the integration of multiomic information, where we found ceramide localization to be correlated with SMPD3 abundance (ceramide synthesis protein), and we also utilized protein abundance to resolve metabolite isomeric ambiguity. Overall, the integration of DESI-MSI into the multiomic workflow allows for complementary spatial and molecular-level information to be achieved from optimized implementations of each MS assay inherent to the workflow itself.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRSDate not supplied

Intracranial Effects of Artificial Gravity: A 3T MRI Study

INTRODUCTION Spaceflight associated neuro-ocular syndrome (SANS) is characterized by the development of optic disc edema, posterior globe flattening, choroidal/retinal folds and hyperopic refractive errors1. SANS is hypothesized to be a result of headward fluid shifts that invariably occurs in the microgravity environment. As a countermeasure, artificial gravity (AG) through centrifugation has been proposed to reduce this headward fluid shift, however there is no current proof of benefit. The goal of this study was to determine if the application of AG can prevent or reduce known changes in brain volumetry, internal carotid artery (ICA) stroke volume and cerebral spinal fluid (CSF) flow velocity that occurs during simulated chronic headward fluid shift using head down tilt bed rest (HDTBR) methodology2 as an indicator of countermeasure efficacy. METHODS Healthy volunteers were recruited for an IRB approved HDTBR study performed at the German Aerospace Center in Cologne, Germany. Strict six-degree HDTBR was used as a spaceflight analog to induce a continuous headward fluid shift. HDTBR was carried out for 60 days for all subjects. Short-arm centrifugation was utilized to generate AG equating to ~0.3g of acceleration at the level of the eye. The subjects were divided equally into three groups: NoAG (control; n=8), daily intermittent AG (6 x 5 min iAG; n=8), and daily continuous 30 min (cAG; n=8). All studies were performed on a single dedicated 3T MRI Scanner. Pulse-gated MRI phase-contrast flow imaging was used to quantify ICA stroke volume and peak-to-peak CSF flow velocity in the mid cerebral aqueduct. 3D-SPGR was acquired for volumetric segmentation of the brain and CSF spaces. MRI acquisitions were obtained at baseline (BDC), 14 days into HDTBR (HDTBR14), 52 days into HDTBR (HDTBR52) and 3-5 days after HDTBR (recovery, R+3/5).The data were analyzed by the mixed model, which included intervention and time (BDC, HDTBR 14, HDTBR 52, R+3/5) as the fixed effects and included subject as the random effect.RESULTS24 healthy subject volunteers (16 men, 8 women, mean age = 33 years ± 9 [standard deviation] and mean BMI = 24.3 kg/m2 ± 2.0) successfully completed all phases of the study. Strict six-degree HDTBR was characterized by progressive and statistically significant (p<.01) increases in mean combined brain and CSF volumes and mean aqueductal CSF peak-to-peak flow velocity, as well as statistically significant (p<.01) progressive decrease in mean ICA stroke volume from baseline to 52 days post intervention (Figs. 1-3). Compared to baseline, only combined brain and CSF volumes did not return to baseline values in the recovery period (p=NS). Neither iAG nor cAG exerted any significant effects on the measured MRI brain parameters as compared to HDTBR alone (p=NS). CONCLUSION Our results indicate that HDTBR at 6-degrees was effective in producing alterations in ICA stroke volume, aqueductal CSF flow velocity, and combined brain and CSF volumetric change that is associated with chronic headward fluid shift. Short duration, 30-min daily exposure to either iAG or cAG appears to be insufficient in preventing or reducing the effects of chronic HDTBR and thus may not be a suitable countermeasure as currently deployed. AG protocol modifications, including increased duration and magnitude of exposure, should be considered for future research.

L A Kramer↗
NASA NTRS1993

Subpixel Resolution In Depth Perceived Via 3-D Television

Report describes experiment in which two black vertical bars on featureless white background placed near intersection of optical axes of two charge-coupled-device video cameras positioned to give stereoscopic views. Trained human observers found to perceive depths at subpixel resolutions in stereoscopic television images. This finding significant for remote stereoscopic monitoring, expecially during precise maneuvers of remotely controlled manipulators. Also significant for research in processing of visual information by human brain.

Diner, Daniel B.↗
NASA NTRS1997

Visuo-Vestibular Interactions

Session TA3 includes short reports covering: (1) Vestibulo-Oculomotor Interaction in Long-Term Microgravity; (2) Effects of Weightlessness on the Spatial Orientation of Visually Induced Eye Movements; (3) Adaptive Modification of the Three-Dimensional Vestibulo-Ocular Reflex during Prolonged Microgravity; (4) The Dynamic Change of Brain Potential Related to Selective Attention to Visual Signals from Left and Right Visual Fields; (5) Locomotor Errors Caused by Vestibular Suppression; and (6) A Novel, Image-Based Technique for Three-Dimensional Eye Measurement.

Source record↗
NASA NTRS1990

Vestibular receptor cells and signal detection: bioaccelerometers and the hexagonal sampling of two-dimensional signals

The inner ear contains sensory organs which signal changes in head movement. The vestibular sacs, in particular, are sensitive to linear accelerations. Electron microscopic images have revealed the structure of tiny sensory hair bundles, whose mechanical deformation results in the initiation of neuronal activity and the transmission of electrical signals to the brain. The structure of the hair bundles is shown in this paper to be that of the most efficient two-dimensional phased-array signal processors.

NASA Program Space Physiology and Countermeasures↗
NASA NTRS2016

The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor functioning. Prolonged exposure to a head-down tilt (HDT) position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with behavior is largely unknown, but of importance to the health and performance of astronauts both during and post-flight. In the present study, we investigate the effects of prolonged exposure to HDT bed rest on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. To validate that our findings were not due to confounding factors such as time or task practice, we also acquired resting state functional magnetic resonance imaging (rs-fMRI) and behavioral measurements from 14 normative control participants at four time points. Bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Rs-fMRI and behavioral data were obtained at seven time points averaging around: 12 and 8 days prior to bed rest; 7, 50, and 70 days during bed rest; and 8 and 12 days after bed rest. 70 days of HDT bed rest resulted in significant increases in functional connectivity during bed rest followed by a reversal of changes in the post bed rest recovery period between motor cortical and somatosensory areas of the brain. In contrast, decreases in connectivity were observed between temporoparietal regions. Furthermore, post-hoc correlation analyses revealed a significant relationship between motor-somatosensory network connectivity and standing balance performance changes; participants that exhibited the greatest increases in connectivity strength showed the least deterioration in postural equilibrium with HDT bed rest. This suggests that neuroplastic processes may facilitate adaptation to the HDT bed rest environment. The findings from this study provide novel insights into the neurobiology and future risk assessments of long-duration spaceflight.

Cassady, K.↗
NASA NTRS1999

Multimodality stereotactic brain tissue identification: the NASA smart probe project

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

Non-programmatic↗
DOE OSTI2023

Vessel Rupture Thresholds for Vessel–Bubble Interactions Using an Earthworm Vasculature Model

Intravenous microbubble oscillation in the presence of ultrasound has the potential to yield a wide range of therapeutic benefits. However, the likelihood of vessel damage caused by mechanical effects has not been quantified as a function of the numerous important parameters in therapeutic ultrasound procedures. In this study, we examined the effects of microbubbles injected into the vasculature of the earthworm. It was found that the elastic properties of earthworm blood vessels are similar to those of arteries in older humans, and that earthworms are well suited to the large number of experiments necessary to investigate safety of procedures involving microbubble oscillation in sonicated vessels. Microbubbles were infused into earthworm vessels, and the rupture time during sonication was recorded as a function of ultrasound frequency, pulse repetition frequency and acoustic pressure. A modified mechanical index (MMI) was defined that successfully captured the trends in rupture probability and rupture time for the different parameter values, creating a database of vessel rupture thresholds. In the absence of bubbles, the product of MMI squared and rupture time was approximately constant, indicating a possible radiation-force effect. Here, the MMI was an effective correlating parameter in the presence of bubbles, though the mathematical dependence is not yet apparent. The results of the study are expected to be valuable in designing more refined studies in vertebrate models, as well as informing computational models.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1995

Neurodynamic oscillators

Oscillation of electrical activity has been found in many nervous systems, from invertebrates to vertebrates including man. There exists experimental evidence of very simple circuits with the capability of oscillation. Neurons with intrinsic oscillation have been found and also neural circuits where oscillation is a property of the network. These two types of oscillations coexist in many instances. It is nowadays hypothesized that behind synchronization and oscillation there is a system of coupled oscillators responsible for activities that range from locomotion and feature binding in vision to control of sleep and circadian rhythms. The huge knowledge that has been acquired on oscillators from the times of Lord Rayleigh has made the simulation of neural oscillators a very active endeavor. This has been enhanced with more recent physiological findings about small neural circuits by means of intracellular and extracellular recordings as well as imaging methods. The future of this interdisciplinary field looks very promising; some researchers are going into quantum mechanics with the idea of trying to provide a quantum description of the brain. In this work we describe some simulations using neuron models by means of which we form simple neural networks that have the capability of oscillation. We analyze the oscillatory activity with root locus method, cross-correlation histograms, and phase planes. In the more complicated neural network models there is the possibility of chaotic oscillatory activity and we study that by means of Lyapunov exponents. The companion paper shows an example of that kind.

Espinosa, Ismael↗
DOE OSTI2024

Patch2Self2: Self-supervised Denoising on Coresets via Matrix Sketching

Diffusion MRI (dMRI) non-invasively maps brain white matter yet necessitates denoising due to low signal-to-noise ratios. Patch2Self (P2S) employing self-supervised techniques and regression on a Casorati matrix effectively denoises dMRI images and has become the new de-facto standard in this field. P2S however is resource intensive both in terms of running time and memory usage as it uses all voxels (n) from all-but-one held-in volumes (d-1) to learn a linear mapping Phi : \mathbb R ^ n x(d-1) \mapsto \mathbb R ^ n for denoising the held-out volume. The increasing size and dimensionality of higher resolution dMRI acquisitions can make P2S infeasible for large-scale analyses. This work exploits the redundancy imposed by P2S to alleviate its performance issues and inspect regions that influence the noise disproportionately. Specifically this study makes a three-fold contribution: (1) We present Patch2Self2 (P2S2) a method that uses matrix sketching to perform self-supervised denoising. By solving a sub-problem on a smaller sub-space so called coreset we show how P2S2 can yield a significant speedup in training time while using less memory. (2) We present a theoretical analysis of P2S2 focusing on determining the optimal sketch size through rank estimation a key step in achieving a balance between denoising accuracy and computational efficiency. (3) We show how the so-called statistical leverage scores can be used to interpret the denoising of dMRI data a process that was traditionally treated as a black-box. Experimental results on both simulated and real data affirm that P2S2 maintains denoising quality while significantly enhancing speed and memory efficiency achieved by training on a reduced data subset.

Fadnavis, Shreyas↗
DOE OSTI2024

Miniature fluorescence sensor for quantitative detection of brain tumour

Fluorescence-guided surgery has emerged as a vital tool for tumour resection procedures. As well as intraoperative tumour visualisation, 5-ALA-induced PpIX provides an avenue for quantitative tumour identification based on ratiometric fluorescence measurement. To this end, fluorescence imaging and fibre-based probes have enabled more precise demarcation between the cancerous and healthy tissues. These sensing approaches, which rely on collecting the fluorescence light from the tumour resection site and its “remote” spectral sensing, introduce challenges associated with optical losses. In this work, we demonstrate the viability of tumour detection at the resection site using a miniature fluorescence measurement system. Unlike the current bulky systems, which necessitate remote measurement, we have adopted a millimetre-sized spectral sensor chip for quantitative fluorescence measurements. A reliable measurement at the resection site requires a stable optical window between the tissue and the optoelectronic system. This is achieved using an antifouling diamond window, which provides stable optical transparency. The system achieved a sensitivity of 92.3% and specificity of 98.3% in detecting a surrogate tumour at a resolution of 1 × 1 mm 2 . In conclusion, as well as addressing losses associated with collecting and coupling fluorescence light in the current ‘remote’ sensing approaches, the small size of the system introduced in this work paves the way for its direct integration with the tumour resection tools with the aim of more accurate interoperative tumour identification.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Collective dynamics and long-range order in thermal neuristor networks

Abstract In the pursuit of scalable and energy-efficient neuromorphic devices, recent research has unveiled a novel category of spiking oscillators, termed “thermal neuristors.” These devices function via thermal interactions among neighboring vanadium dioxide resistive memories, emulating biological neuronal behavior. Here, we show that the collective dynamical behavior of networks of these neurons showcases a rich phase structure, tunable by adjusting the thermal coupling and input voltage. Notably, we identify phases exhibiting long-range order that, however, does not arise from criticality, but rather from the time non-local response of the system. In addition, we show that these thermal neuristor arrays achieve high accuracy in image recognition and time series prediction through reservoir computing, without leveraging long-range order. Our findings highlight a crucial aspect of neuromorphic computing with possible implications on the functioning of the brain: criticality may not be necessary for the efficient performance of neuromorphic systems in certain computational tasks.

Science & Technology - Other Topics↗
NASA NTRS1964

Glycogen in the Nervous System: Methods for Light and Electron Microscopy - I

'l'he relative value of different methods for combined light and electron microscopical studies of glycogen in the nervous tissue was investigated. Picroalcoholic fixatives preserve glycogen in a considerable amount but give an inadequate morphological image of glycogen distribution and are unsuitable for ultrastructural studies. Fixation by perfusion, with Dalton's chromeosmic fluid seems adequate for ultrastructural cytochemistry of glycogen. Furthermore it permits routine paraffin embedding of brain slices adjacent to those used for electron microscopy. Dimedone blocking is a necessary step for a selective staining of glycogen with PAS after osmic fixation. Enzymatic removal of glycogen in osmic fixed nervous tissue can be done In paraffin-embedded tissue. It can also be performed in glycolmethacrylate-embedded tissue without removal of the embedding medium. Paraphenylenediamine stains glycogen following periodic acid oxidation.

Estable, Rosita F. De↗