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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study was to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts were recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests included assessments of sensory dependency and adaptability. Visual dependency involved treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds were measured while seated during lateral translations. Proprioception dependency was measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability was performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms (adaptive Functional Mobility Test, aFMT). The neuroimaging tests characterized individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests utilized saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Thirty ISS crewmembers were recruited, including 12 first-time fliers, 6F, and mission durations lasting 185.5 ± 45.5 days, mean ± std. We utilized a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There was considerable variability among all post-flight performance outcomes. Based on an ordinal scale survey, 72% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. Understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

biomarkers↗
NASA NTRS1993

Measuring the metastatic potential of cancer cells

Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

Morrison, Dennis R.↗
NASA NTRSDate not supplied

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms. The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-one ISS crewmembers have been tested to date, including 6 from this past year after testing resumed post-COVID. This cohort includes 9 first-time fliers, 4F, and mission durations lasting 182 ± 32 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 21 participants to date. Based on a partial sample using an ordinal scale survey, 80% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures; however, additional data is needed to draw conclusions. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

S J Wood↗
NASA NTRS2024

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed(1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms(adaptive Functional Mobility Test, aFMT). The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure(using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-seven ISS crewmembers have been tested to date, including 6 from this past year. This cohort includes 10first-time fliers, 6F, and mission durations lasting 178.6 ± 30.5 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 27participants to date. Based on a partial sample using an ordinal scale survey, 70% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures, e.g., the cumulative time to complete the aFMT is significantly correlated to pre-to-post-flight changes in tandem walk (rho= 0.64, p = 0.001). Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures

S J Wood↗
NASA NTRS2013

Mobile In Vivo Infrared Data Collection and Diagnoses Comparison System

Described is a mobile in vivo infrared brain scan and analysis system. The system includes a data collection subsystem and a data analysis subsystem. The data collection subsystem is a helmet with a plurality of infrared (IR) thermometer probes. Each of the IR thermometer probes includes an IR photodetector capable of detecting IR radiation generated by evoked potentials within a user's skull. The helmet is formed to collect brain data that is reflective of firing neurons in a mobile subject and transmit the brain data to the data analysis subsystem. The data analysis subsystem is configured to generate and display a three-dimensional image that depicts a location of the firing neurons. The data analysis subsystem is also configured to compare the brain data against a library of brain data to detect an anomaly in the brain data, and notify a user of any detected anomaly in the brain data.

Mintz, Frederick W.↗
DOE OSTI2026

Operando microscopy for neuromorphic hardware

Microscopy techniques can uncover the physical properties and dynamic behaviours of materials, driving the discovery of emergent phenomena and guiding the design of next-generation computing hardware. As artificial intelligence becomes pervasive, the demand for high-performance materials to support sustainable information technologies is growing. Here, this Review highlights state-of-the-art imaging from electron and X-ray to optical techniques to probe the dynamics of neuromorphic materials, including operando characterization of devices. We examine design principles for neuromorphic materials, along with obstacles that hinder their development. Emphasis is placed on spatially and temporally resolved approaches that capture state changes including phase transitions, ferroic switching and spin-wave propagation that emulate biological components such as neurons, synapses and their connectivity. We discuss challenges in operando characterization and the integration of artificial intelligence-driven analysis for feedback-guided material discovery. Finally, we outline opportunities for real-time imaging of neuromorphic systems, paving the way towards adaptive, brain-inspired hardware.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2021

Boosting the signal-to-noise of low-field MRI with deep learning image reconstruction

Recent years have seen a resurgence of interest in inexpensive low magnetic field (< 0.3 T) MRI systems mainly due to advances in magnet, coil and gradient set designs. Most of these advances have focused on improving hardware and signal acquisition strategies, and far less on the use of advanced image reconstruction methods to improve attainable image quality at low field. We describe here the use of our end-to-end deep neural network approach (AUTOMAP) to improve the image quality of highly noise-corrupted low-field MRI data. We compare the performance of this approach to two additional state-of-the-art denoising pipelines. We find that AUTOMAP improves image reconstruction of data acquired on two very different low-field MRI systems: human brain data acquired at 6.5 mT, and plant root data acquired at 47 mT, demonstrating SNR gains above Fourier reconstruction by factors of 1.5- to 4.5-fold, and 3-fold, respectively. In these applications, AUTOMAP outperformed two different contemporary image-based denoising algorithms, and suppressed noise-like spike artifacts in the reconstructed images. The impact of domain-specific training corpora on the reconstruction performance is discussed. The AUTOMAP approach to image reconstruction will enable significant image quality improvements at low-field, especially in highly noise-corrupted environments.

42 ENGINEERING↗
NASA NTRS1976

Superconductive neuristor R-junction

Device incorporating specially-configured pure metal transition region can be developed to simulate a nerve cell. Combination of such cells may be formed to simulate an eye or brain and can be used in recognizing characters and other visual images.

Reible, S. A.↗
NASA NTRS1984

The APL image processing laboratory

The present and proposed capabilities of the Central Image Processing Laboratory, which provides a powerful resource for the advancement of programs in missile technology, space science, oceanography, and biomedical image analysis, are discussed. The use of image digitizing, digital image processing, and digital image output permits a variety of functional capabilities, including: enhancement, pseudocolor, convolution, computer output microfilm, presentation graphics, animations, transforms, geometric corrections, and feature extractions. The hardware and software of the Image Processing Laboratory, consisting of digitizing and processing equipment, software packages, and display equipment, is described. Attention is given to applications for imaging systems, map geometric correction, raster movie display of Seasat ocean data, Seasat and Skylab scenes of Nantucket Island, Space Shuttle imaging radar, differential radiography, and a computerized tomographic scan of the brain.

Jenkins, J. O.↗
NASA NTRS1999

Deblurring

In most instances, traditional EEG methodology provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. This article describes a method called Deblurring for increasing the spatial detail of the EEG and for fusing neurophysiologic and neuroanatomic data. Deblurring estimates potentials near the outer convexity of the cortex using a realistic finite element model of the structure of a subject's head determined from their magnetic resonance images. Deblurring is not a source localization technique and thus makes no assumptions about the number or type of generator sources. The validity of Deblurring has been initially tested by comparing deblurred data with potentials measured with subdural grid recordings. Results suggest that deblurred topographic maps, registered with a subject's magnetic resonance imaging and rendered in three dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. Example results are presented from research studies of somatosensory stimulation, movement, language, attention and working memory. Deblurred ictal EEG data are also presented, indicating that this technique may have future clinical application as an aid to seizure localization and surgical planning.

Non-NASA Center↗
DOE OSTI2020

Parallel high-frequency magnetic sensing with an array of flux transformers and multi-channel optically pumped magnetometer for hand MRI application

Here, we investigate an approach for parallel high-frequency magnetic sensing based on a multi-channel radio frequency (RF) optically pumped magnetometer (OPM) coupled to multiple flux transformers (FTs) with a focus on hand magnetic resonance imaging (MRI) application at ultra-low field (ULF). Multiple RF OPM sensing channels are realized by using a single large-area alkali-metal vapor cell and two laser beams for pumping and probing, shared for all the channels. This design leads to significant cost reduction when multi-channel sensing is desirable, as in the case of ULF MRI. The FT, composed of two connected coils, serves as a transmitter of a target magnetic field to the OPM, while decoupling the OPM from untargeted magnetic fields in the sensing area that can limit the OPM performance. For hand MRI application, theoretical and numerical analysis is performed to determine an optimal geometry for the FT array that could improve signal-to-noise ratio (SNR) and sufficiently reduce crosstalk between FTs. We estimate that the optimized multi-channel FT-OPM sensor can achieve a magnetic field sensitivity of the order of 1 fT / Hz 1 / 2 above 100 kHz, which would be sufficient for 1 mm resolution MRI. In general, the multi-channel capability enables simultaneous magnetic measurements, thus reducing the sensing time and improving the SNR, and we anticipate many applications of the multi-channel FT-OPM sensor beyond the targeted here hand MRI: anatomical parallel ULF MRI of the human brain and other parts of the body, airport security screening, magnetic material imaging, and many others.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
NASA NTRS2016

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

The current study characterizes 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 either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. 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 otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. 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 myogenic potentials, indicated by eye muscle responses. We further assessed subjects' postural control and its correlation with vestibular cortical activity. Our results provide the first evidence of using skull taps to elicit vestibular activity inside the MRI scanner. By conducting conjunction analyses we showed that skull taps elicit the same activation pattern as auditory tone bursts (superior temporal gyrus), and both modes of stimulation activate previously identified vestibular cortical regions. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects. This further supports that the skull tap could replace auditory tone burst stimulation in clinical interventions and basic science research. Moreover, we observed that greater vestibular activation is associated with better balance control. We showed that not only the quality of balance (indicated by the amount of body sway) but also the ability to maintain balance for a longer time (indicated by the balance time) was associated with individuals' vestibular cortical excitability. Our findings support an association between vestibular cortical activity and individual differences in balance. In sum, we found that the skull tap stimulation results in activation of canonical vestibular cortex, suggesting an equally valid, but more tolerable stimulation method compared to auditory tone bursts. This is of high importance in longitudinal vestibular assessments, in which minimizing aversive effects may contribute to higher protocol adherence.

Noohi, F.↗
DOE OSTI2020

Label-free X-ray estimation of brain amyloid burden

Amyloid plaque deposits in the brain are indicative of Alzheimer’s and other diseases. Measurements of brain amyloid burden in small animals require laborious post-mortem histological analysis or resource-intensive, contrast-enhanced imaging techniques. We describe a label-free method based on spectral small-angle X-ray scattering with a polychromatic beam for in vivo estimation of brain amyloid burden. Our findings comparing 5XFAD versus wild-type mice correlate well with histology, showing promise for a fast and practical in vivo technique.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2015

The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor systems and neurocognitive performance. Prolonged exposure to a head-down tilt 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 neurocognitive performance is largely unknown, but of potential importance to the health and performance of astronauts both during and post-flight. The aims of the present study are 1) to identify changes in sensorimotor resting state functional connectivity that occur with extended bed rest exposure, and to characterize their recovery time course; 2) to evaluate how these neural changes correlate with neurocognitive performance. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected from 17 male participants. The data were acquired through the NASA bed rest facility, located at the University of Texas Medical Branch (Galveston, TX). Participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. RsfMRI data were obtained at seven time points: 7 and 12 days before bed rest; 7, 50, and 65 days during bed rest; and 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (fcMRI) analysis was performed to measure the connectivity of sensorimotor networks in the brain before, during, and post-bed rest. We found a decrease in left putamen connectivity with the pre- and post-central gyri from pre bed rest to the last day in bed rest. In addition, vestibular cortex connectivity with the posterior cingulate cortex decreased from pre to post bed rest. Furthermore, connectivity between cerebellar right superior posterior fissure and other cerebellar regions decreased from pre bed rest to the last day in bed rest. In contrast, connectivity within the default mode network remained stable over the course of bed rest. We also utilized a battery of behavioral measures including spatial working memory tasks and measures of functional mobility and balance. These behavioral measurements were collected before, during, and after bed rest. We will report the preliminary findings of correlations observed between brain functional connectivity and behavioral performance changes. Our results suggest that sensorimotor brain networks exhibit decoupling with extended periods of reduced usage. The findings from this study could aid in the understanding and future design of targeted countermeasures to alleviate the detrimental health and neurocognitive effects of long-duration spaceflight.

Cassady, K.↗
NASA NTRS2001

Stimulus-response incompatibility activates cortex proximate to three eye fields

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory. Copyright 2001 Academic Press.

NASA Discipline Neuroscience↗
DOE OSTI2024

Laminography as a tool for imaging large-size samples with high resolution

Despite the increased brilliance of the new generation synchrotron sources, there is still a challenge with high-resolution scanning of very thick and absorbing samples, such as a whole mouse brain stained with heavy elements, and, extending further, brains of primates. Samples are typically cut into smaller parts, to ensure a sufficient X-ray transmission, and scanned separately. Compared with the standard tomography setup where the sample would be cut into many pillars, the laminographic geometry operates with slab-shaped sections significantly reducing the number of sample parts to be prepared, the cutting damage and data stitching problems. In this work, a laminography pipeline for imaging large samples (>1 cm) at micrometre resolution is presented. The implementation includes a low-cost instrument setup installed at the 2-BM micro-CT beamline of the Advanced Photon Source. Additionally, sample mounting, scanning techniques, data stitching procedures, a fast reconstruction algorithm with low computational complexity, and accelerated reconstruction on multi-GPU systems for processing large-scale datasets are presented. The applicability of the whole laminography pipeline was demonstrated by imaging four sequential slabs throughout an entire mouse brain sample stained with osmium, in total generating approximately 12 TB of raw data for reconstruction.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

Electrochemically modulated single-molecule localization microscopy for in vitro imaging cytoskeletal protein structures

A new concept of electrochemically modulated single-molecule localization super-resolution imaging is developed. Applications of single-molecule localization super-resolution microscopy have been limited due to insufficient availability of qualified fluorophores with favorable low duty cycles. The key for the new concept is that the “On” state of a redox-active fluorophore with unfavorable high duty cycle could be driven to “Off” state by electrochemical potential modulation and thus become available for single-molecule localization imaging. The new concept was carried out using redox-active cresyl violet with unfavorable high duty cycle as a model fluorophore by synchronizing electrochemical potential scanning with a single-molecule localization microscope. The two cytoskeletal protein structures, the microtubules from porcine brain and the actins from rabbit muscle, were selected as the model target structures for the conceptual imaging in vitro. The super-resolution images of microtubules and actins were obtained from precise single-molecule localizations determined by modulating the On/Off states of single fluorophore molecules on the cytoskeletal proteins via electrochemical potential scanning. Importantly, this method could allow more fluorophores even with unfavorable photophysical properties to become available for a wider and more extensive application of single-molecule localization microscopy.

electrochemical modulation↗
DOE OSTI2021

Topological data analysis of task-based fMRI data from experiments on schizophrenia

We use methods from computational algebraic topology to study functional brain networks, in which nodes represent brain regions and weighted edges represent similarity of fMRI time series from each region. With these tools, which allow one to characterize topological invariants such as loops in high-dimensional data, we are able to gain understanding into low-dimensional structures in networks in a way that complements traditional approaches based on pairwise interactions. In the present paper, we analyze networks constructed from task-based fMRI data from schizophrenia patients, healthy controls, and healthy siblings of schizophrenia patients using persistent homology, which allows us to explore the persistence of topological structures such as loops at different scales in the networks. We use persistence landscapes, persistence images, and Betti curves to create output summaries from our persistent-homology calculations, and we study the persistence landscapes and images using k-means clustering and community detection. Based on our analysis of persistence landscapes, we find that the members of the sibling cohort have topological features (specifically, their 1-dimensional loops) that are distinct from the other two cohorts. From the persistence images, we are able to distinguish all three subject groups and to determine the brain regions in the loops (with four or more edges) that allow us to make these distinctions.

60 APPLIED LIFE SCIENCES↗