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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Analysis and visualization of single-trial event-related potentials

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data. Copyright 2001 Wiley-Liss, Inc.

Non-NASA Center↗
NASA NTRS2008

Using Electronic Noses to Detect Tumors During Neurosurgery

It has been proposed to develop special-purpose electronic noses and algorithms for processing the digitized outputs of the electronic noses for determining whether tissue exposed during neurosurgery is cancerous. At present, visual inspection by a surgeon is the only available intraoperative technique for detecting cancerous tissue. Implementation of the proposal would help to satisfy a desire, expressed by some neurosurgeons, for an intraoperative technique for determining whether all of a brain tumor has been removed. The electronic-nose technique could complement multimodal imaging techniques, which have also been proposed as means of detecting cancerous tissue. There are also other potential applications of the electronic-nose technique in general diagnosis of abnormal tissue. In preliminary experiments performed to assess the viability of the proposal, the problem of distinguishing between different types of cultured cells was substituted for the problem of distinguishing between normal and abnormal specimens of the same type of tissue. The figure presents data from one experiment, illustrating differences between patterns that could be used to distinguish between two types of cultured cancer cells. Further development can be expected to include studies directed toward answering questions concerning not only the possibility of distinguishing among various types of normal and abnormal tissue but also distinguishing between tissues of interest and other odorous substances that may be present in medical settings.

Homer, Margie L.↗
DOE OSTI2025

Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam

Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. Here, we performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Kay, Tyler V. [Duke University, Durham, NC (United↗
DOE OSTI2021

Mixture Model Framework for Traumatic Brain Injury Prognosis Using Heterogeneous Clinical and Outcome Data

Prognoses of Traumatic Brain Injury (TBI) outcomes are neither easily nor accurately determined from clinical indicators. This is due in part to the heterogeneity of damage inflicted to the brain, ultimately resulting in diverse and complex outcomes. Using a data-driven approach on many distinct data elements may be necessary to describe this large set of outcomes and thereby robustly depict the nuanced differences among TBI patients’ recovery. In this work, we develop a method for modeling large heterogeneous data types relevant to TBI. Our approach is geared toward the probabilistic representation of mixed continuous and discrete variables with missing values. The model is trained on a dataset encompassing a variety of data types, including demographics, blood-based biomarkers, and imaging findings. In addition, it includes a set of clinical outcome assessments at 3, 6, and 12 months post-injury. The model is used to stratify patients into distinct groups in an unsupervised learning setting. We use the model to infer outcomes using input data, and show that the collection of input data reduces uncertainty of outcomes over a baseline approach. In addition, we quantify the performance of a likelihood scoring technique that can be used to self-evaluate the extrapolation risk of prognosis on unseen patients.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model.

Abstract Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin.

Pushie, M. J. (ORCID:0000000174945427)↗
DOE OSTI2020

Development of Lipid-Coated Semiconductor Nanosensors for Recording of Membrane Potential in Neurons

In the past decade, optical imaging methods have significantly improved our understanding of the information processing principles in the brain. Although many promising tools have been designed, sensors of membrane potential are lagging behind the rest. Semiconductor nanoparticles are an attractive alternative to classical voltage indicators, such as voltage-sensitive dyes and proteins. Such nanoparticles exhibit high sensitivity to external electric fields via the quantum-confine Stark effect. Here we report the development of semiconductor voltage-sensitive nanorods (vsNRs) that self-insert into the neuronal membrane. To facilitate interaction of the nanorods with the membrane, we functionalized their surface with the lipid mixture derived from brain extract. We describe a workflow to detect and process the photoluminescent signal of vsNRs after widefield time-lapse recordings. We also present data indicating that vsNRs are feasible for sensing membrane potential in neurons at a single-particle level. This shows the potential of vsNRs for the detection of neuronal activity with unprecedentedly high spatial and temporal resolution.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2001

'The surface management system' (SuMS) database: a surface-based database to aid cortical surface reconstruction, visualization and analysis

Surface reconstructions of the cerebral cortex are increasingly widely used in the analysis and visualization of cortical structure, function and connectivity. From a neuroinformatics perspective, dealing with surface-related data poses a number of challenges. These include the multiplicity of configurations in which surfaces are routinely viewed (e.g. inflated maps, spheres and flat maps), plus the diversity of experimental data that can be represented on any given surface. To address these challenges, we have developed a surface management system (SuMS) that allows automated storage and retrieval of complex surface-related datasets. SuMS provides a systematic framework for the classification, storage and retrieval of many types of surface-related data and associated volume data. Within this classification framework, it serves as a version-control system capable of handling large numbers of surface and volume datasets. With built-in database management system support, SuMS provides rapid search and retrieval capabilities across all the datasets, while also incorporating multiple security levels to regulate access. SuMS is implemented in Java and can be accessed via a Web interface (WebSuMS) or using downloaded client software. Thus, SuMS is well positioned to act as a multiplatform, multi-user 'surface request broker' for the neuroscience community.

NASA Discipline Neuroscience↗
DOE OSTI2021

A NIR fluorescent smart probe for imaging tumor hypoxia

Abstract Background Tumor hypoxia is a characteristic of paramount importance due to low oxygenation levels in tissue negatively correlating with resistance to traditional therapies. The ability to noninvasively identify such could provide for personalized treatment(s) and enhance survival rates. Accordingly, we recently developed an NIR fluorescent hypoxia‐sensitive smart probe ( NO 2 ‐Rosol ) for identifying hypoxia via selectively imaging nitroreductase (NTR) activity, which could correlate to oxygen deprivation levels in cells, thereby serving as a proxy. We demonstrated proof of concept by subjecting a glioblastoma (GBM) cell line to extreme stress by evaluating such under radiobiological hypoxic ( p O 2 ≤ ~0.5%) conditions, which is a far cry from representative levels for hypoxia for brain glioma ( p O 2 = ~1.7%) which fluctuate little from physiological hypoxic ( p O 2 = 1.0‐3.0%) conditions. Aim We aimed to evaluate the robustness, suitability, and feasibility of NO 2 ‐Rosol for imaging hypoxia in vitro and in vivo via assessing NTR activity in diverse GBM models under relevant oxygenation levels ( p O 2 = 2.0%) within physiological hypoxic conditions that mimic oxygenation levels in GBM tumor tissue in the brain. Methods We evaluated multiple GBM cell lines to determine their relative sensitivity to oxygenation levels via measuring carbonic anhydrase IX (CAIX) levels, which is a surrogate marker for indirectly identifying hypoxia by reporting on oxygen deprivation levels and upregulated NTR activity. We evaluated for hypoxia via measuring NTR activity when employing NO 2 ‐Rosol in in vitro and tumor hypoxia imaging studies in vivo. Results The GBM39 cell line demonstrated the highest CAIX expression under hypoxic conditions representing that of GBM in the brain. NO 2 ‐Rosol displayed an 8‐fold fluorescence enhancement when evaluated in GBM39 cells ( p O 2 = 2.0%), thereby establishing its robustness and suitability for imaging hypoxia under relevant physiological conditions. We demonstrated the feasibility of NO 2 ‐Rosol to afford tumor hypoxia imaging in vivo via it demonstrating a tumor‐to‐background of 5 upon (i) diffusion throughout, (ii) bioreductive activation by NTR activity in, and (iii) retention within, GBM39 tumor tissue. Conclusion We established the robustness, suitability, and feasibility of NO 2 ‐Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.

Hettie, Kenneth S.↗
NASA NTRS2014

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory tone burst elicited vestibular evoked activation, indicated by eye muscle response. Our preliminary analyses showed that the skull tap elicited activation in medial frontal gyrus, superior temporal gyrus, postcentral gyrus, transverse temporal gyrus, anterior cingulate, and putamen. The auditory tone bursts elicited activation in medial frontal gyrus, superior temporal gyrus, superior frontal gyrus, precentral gyrus, inferior and superior parietal lobules. In line with our hypothesis, skull taps elicited a pattern of cortical activity closely similar to one elicited by auditory tone bursts. Further analysis will determine the extent to which the skull taps can replace the auditory tone stimulation in clinical and basic science vestibular assessments.

Noohi, Fatemeh↗
DOE OSTI2022

High-Frequency 3D Photoacoustic Computed Tomography Using an Optical Microring Resonator

3D photoacoustic computed tomography (3D-PACT) has made great advances in volumetric imaging of biological tissues, with high spatial-temporal resolutions and large penetration depth. The development of 3D-PACT requires high-performance acoustic sensors with a small size, large detection bandwidth, and high sensitivity. In this work, we present a new high-frequency 3D-PACT system that uses a microring resonator (MRR) as the acoustic sensor. The MRR sensor has a size of 80 μ m in diameter and was fabricated using the nanoimprint lithography technology. Using the MRR sensor, we have developed a transmission-mode 3D-PACT system that has achieved a detection bandwidth of ~23 MHz, an imaging depth of ~8 mm, a lateral resolution of 114 μ m, and an axial resolution of 57 μ m. We have demonstrated the 3D PACT’s performance on in vitro phantoms, ex vivo mouse brain, and in vivo mouse ear and tadpole. The MRR-based 3D-PACT system can be a promising tool for structural, functional, and molecular imaging of biological tissues at depths.

47 OTHER INSTRUMENTATION↗
NASA NTRS1975

Biocybernetic factors in human perception and memory

The objective of this research is to develop biocybernetic techniques for use in the analysis and development of skills required for the enhancement of concrete images of the 'eidetic' type. The scan patterns of the eye during inspection of scenes are treated as indicators of the brain's strategy for the intake of visual information. The authors determine the features that differentiate visual scan patterns associated with superior imagery from scan patterns associated with inferior imagery, and simultaneously differentiate the EEG features correlated with superior imagery from those correlated with inferior imagery. A closely-coupled man-machine system has been designed to generate image enhancement and to train the individual to exert greater voluntary control over his own imagery. The models for EEG signals and saccadic eye movement in the man-machine system have been completed. The report describes the details of these models and discusses their usefulness.

Lai, D. C.↗
DOE OSTI2023

pnnl/brain_ohsu

Light sheet microscopy has made possible the 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. We fine-tuned an existing model, TrailMap, using expert labeled data from axonal structures in neocortex. Without changing the network architecture, we implemented nnU-Net framework modifications in data augmentation, data foreground sampling, window learning rate, and the inference overlap method. The resulting model from these combined approaches yielded an improved F1 score

Oostrom, Marjolein↗
DOE OSTI2024

Fine-tuning TrailMap: The utility of transfer learning to improve the performance of deep learning in axon segmentation of light-sheet microscopy images

Light-sheet microscopy has made possible the 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual undertaking. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through optimizing transfer learning. We fine-tuned the existing TrailMap model using expert-labeled data from noradrenergic axonal structures in the mouse brain. By changing the cross-entropy weights and using augmentation, we demonstrate a generally improved adjusted F1-score over using the originally trained TrailMap model within our test datasets.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Data-driven Mapping of the Mouse Connectome: The utility of transfer learning to improve the performance of deep learning models performing axon segmentation on light-sheet microscopy images

Light sheet microscopy has made possible the high temporal and spatial 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual process. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through the application of refinements such as transfer learning.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Susceptibility weighted MRI pinpoints spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats

Purpose: To find magnetic resonance imaging (MRI) precursors of spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats (SHRSP). Method: SHRSP rats were used with both a low/high salt (n = 18 or 11) Japanese diet and salty drinking water to generate spontaneous intracerebral hemorrhage (ICH). Various MRI sequences, and in particular, susceptibility weighted imaging (SWI), were used and combined with a gadolinium (Gd) contrast agent or oxygen gas to identify the rupture of the blood brain barrier (BBB) and the temporal ICH. Results: Most rats developed hypertensive ICH stroke in the high salt group during the 10–13 week period compared to only one third of rats in the low salt group during the 14–18 week period. The location of stroke for both the low/high-salt groups was highest in the striatum (58%/43%), followed by the cortex (21%/30%). The edematous enhancement on T2 weighted (T2W) imaging or Gd based T1 weighted (Gd-T1W) imaging due to the ruptured BBB preceded the striatal hemorrhages seen on SWI. The most recent bleeds were observed on temporal SWI or on oxygen-enhanced SWI. The mode of the volume of bleeds was 0.4 mm 3 . A positive correlation between susceptibility x volume and R2* x volume of the bleeds was observed. Conclusions: SHRSP rats with the high salt diet effectively generated a hypertensive hemorrhagic stroke which could be monitored by various MRI sequences. The venous dilation on SWI may precede any abnormality on T2W or Gd-T1W imaging. The edematous enhancement on T2W or Gd-T1W indicated a BBB breakdown that may precede striatal ICH by several days. This suggests the need for immediate treatment to improve outcome if this finding is observed. Here, the use of oxygen with SWI was able to help differentiate old bleeds from very recent bleeds.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2002

A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation

Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired NIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1/BOLD) (approximately R(2)(*)) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the NIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIRS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation.

Non-NASA Center↗
DOE OSTI2022

Physical Models from Physical Templates Using Biocompatible Liquid Crystal Elastomers as Morphologically Programmable Inks For 3D Printing

Advanced manufacturing has received considerable attention as a tool for the fabrication of cell scaffolds however, finding ideal biocompatible and biodegradable materials that fit the correct parameters for 3D printing and guide cells to align remain a challenge. Herein, a photocrosslinkable smectic-A (Sm-A) liquid crystal elastomer (LCE) designed for 3D printing is presented, that promotes cell proliferation but most importantly induces cell anisotropy. The LCE-based bio-ink allows the 3D duplication of a highly complex brain structure generated from an animal model. Vascular tissue models are generated from fluorescently stained mouse tissue spatially imaged using confocal microscopy and subsequently processed to create a digital 3D model suitable for printing. The 3D structure is reproduced using a Digital Light Processing (DLP) stereolithography (SLA) desktop 3D printer. Synchrotron Small-Angle X-ray Diffraction (SAXD) data reveal a strong alignment of the LCE layering within the struts of the printed 3D scaffold. The resultant anisotropy of the LCE struts is then shown to direct cell growth. This study offers a simple approach to produce model tissues built within hours that promote cellular alignment.

3D cell culture↗