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All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Development of a Point of Care Technology for Military Medical Applications in Austere Environments

NASA, Lawrence Livermore National Laboratory (LLNL) and the Department of Defense (DoD) share a common interest in compact medical diagnostic technologies—also known as “point of care testing” (POCT) technologies. For NASA, the need is to take care of astronauts on deep space missions. For LLNL, the focus is on technologies needed to support homeland security applications. For DoD, the need is to support warfighters in military theaters of operation, especially for prolonged field care and en route care. A recently patented technology, “Portable Medical Diagnosis Instrument” (U.S. Patent 9824870), co-invented by NASA and LLNL, is being developed further in a partnership between NASA, LLNL and Travis Air Force Base, with a focus on military applications. This instrument, the NASA-LLNL Medical Tricorder, can be used for a wide range of clinical samples including breath, saliva and blood. One component of the Tricorder is the NASA E-Nose, a carbon nanotube-based chemical sensor, integrated into a hand-held smart phone, that can detect and measure “breath biomarkers” in the gas phase of exhaled breath. The response of the NASA E-Nose is rapid, which makes it possible to detect various gas-phase substances in real time. The NASA E-Nose, with modification, can also be used for breath condensate analysis. Another component of the Tricorder is a miniaturized microfluidic analyzer, under development by LLNL, that does not require any pumps. The microfluidic analyzer can detect and measure biomarkers in liquid samples, such as blood, saliva and breath condensate. This microfluidic system requires small quantities of liquid sample and can perform analysis very rapidly (seconds to minutes), which makes it possible to detect relevant biomarkers in near real time in the field. The Clinical Investigation Facility (CIF) at Travis Air Force Base is currently conducting research with the goal to develop improved field-able technologies and procedures for the emergency response to life threatening injuries soldiers may receive in theater. This work includes experimental large animal systems and comprehensive collection of clinical specimens and physiological data. NASA and LLNL are partnering with Travis to test and further develop the Tricorder technology for high priority military applications, initially focused on lung injury models and traumatic brain injury.

Loftus, David J.↗
DOE OSTI2026

Nicotinamide-Loaded Peptoid Nanotubes for Energy Regeneration in Acute Brain Injury

Acute brain injuries such as perinatal asphyxia, stroke, and traumatic brain injury result in ischemia, oxidative stress, excitotoxicity, and inflammation, leading to a depletion of ATP. Nicotinamide adenine dinucleotide (NAD+) is crucial for ATP regeneration and DNA repair during postinjury recovery. However, the therapeutic benefits of NAD+ and its precursors, such as nicotinamide (NAM), are limited by challenges in achieving effective cell-specific intracellular delivery. In this study, we use a nanopeptoid delivery strategy to replenish the cellular redox state and increase energy production in the acutely injured brain. By self-assembling peptoids into tubular structures, we created biocompatible NAM-conjugated peptoid nanotubes (NAM-PNTs) that vary in tubular length. NAM-PNTs demonstrated significant therapeutic benefits by enhancing cell viability and replenishing intracellular ATP levels within 24 h of treatment in oxygen–glucose-deprived (OGD) BV-2 cells. In organotypic brain slices, NAM-PNT treatment promoted glial proliferation, reduced proinflammatory cytokines, and increased anti-inflammatory cytokines after OGD, an ex vivo model of hypoxia-ischemia. The effect of NAM-PNTs is associated with their uptake into microglia via fluid-phase phagocytosis and caveolae-mediated endocytosis. A single systemic dose of NAM-PNTs localized in microglia in the injured hemisphere and reduced brain tissue loss and improved neuropathology after hypoxia-ischemia in term-equivalent rats. These findings highlight the therapeutic potential of NAM-PNTs for cell-specific targeted delivery and energy restoration in the acutely injured neonatal brain. In the neonatal brain injury field, this work demonstrates the development of an innovative nanoparticle platform from first-principles design and synthesis to in vitro screening and then demonstration of efficacy in vivo .

ATP↗
DOE OSTI2023

Normative Ranges for, and Interrater Reliability of, Rotational Vestibular and Balance Tests in U.S. Military Service Members and Veterans

Purpose: The objectives of this study were to (a) describe normative ranges—expressed as reference intervals (RIs)—for vestibular and balance function tests in a cohort of Service Members and Veterans (SMVs) and (b) to describe the interrater reliability of these tests. Method: As part of the Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury (TBI) Study, participants completed the following: vestibulo-ocular reflex suppression, visual-vestibular enhancement, subjective visual vertical, subjective visual horizontal, sinusoidal harmonic acceleration, the computerized rotational head impulse test (crHIT), and the sensory organization test. RIs were calculated using nonparametric methods and interrater reliability was assessed using intraclass correlation coefficients between three audiologists who independently reviewed and cleaned the data. Results: Reference populations for each outcome measure comprised 40 to 72 individuals, 19 to 61 years of age, who served either as noninjured controls (NIC) or injured controls (IC) in the 15-year study; none had a history of TBI or blast exposure. A subset of 15 SMVs from the NIC, IC, and TBI groups were included in the interrater reliability calculations. RIs are reported for 27 outcome measures from the seven rotational vestibular and balance tests. Interrater reliability was considered excellent for all tests except the crHIT, which was found to have good interrater reliability. Conclusion: This study provides clinicians and scientists with important information regarding normative ranges and interrater reliability for rotational vestibular and balance tests in SMVs.

Audiology & Speech-Language Pathology↗
DOE OSTI2022

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Blunt Impact Brain Injury using Cellular Injury Criterion

The Advanced Combat Helmet (\ACH") military specification (\mil-spec") requires a helmeted magnesium (\Mg") Department of Transportation (\DOT") headform be dropped vertically, with an impact speed of 3.1 m/s (10 ft/s), onto a steel hemispherical target. The pass/fail criteria are based on translational acceleration (150 G) alone, absent of any rotational component. Without a rotational component, the specification's injury risk application is limited to skull fracture and peripheral hematomas (subdural, subarachnoid), since this translational acceleration injury risk assessment is based on the Wayne State Tolerance Curve (\WSTC"). To provide a more comprehensive view of injury for the entire brain, an alternative approach is needed. To meet this need, we worked with a larger group called PANTHER, a collaboration between national laboratories, industry, and academia. Collaborations specific to research and results presented here come from efforts led by Mr. Ron Szalkowski and Mr. Sushant Malave, Ms. Alice Fawzi, and Dr. Christian Franck. We have developed a prototypical injury risk criterion based on the neuronal response to abrupt changes in general motion (translation, rotation, or both). The cellular-based mild traumatic brain injury (\cbmTBI") criterion utilizes both the strain and strain rate of brain tissue to account for the stretch and rate of stretch that occurs throughout the brain as a result of blunt impact to the head. We conducted physical experiments of an ACH-fitted magnesium headform, which produced repeatable headform peak accelerations. Then, we developed a simulation of the experiment, and validated the simulation output with the experimental data. We then substituted the magnesium headform with a human headform, consisting of skin, muscle, bone, gray matter, white matter, cerebral-spinal fluid, membranes, vasculature, intravertebral discs, airway and sinus. We quantified brain injury risk using the cbmTBI criterion, using the current mil-spec test and a modified test. The modified mil-spec test used an inclined anvil target that was located posterior to the crown of the helmet in the axial plane. While the current mil-spec test produced brain deformation from head translation alone, the modified test produced brain deformation from head translation and rotation, which is closer to most real world and combat theater impacts (e.g., such as occur in tertiary blast exposure). Compared to the current mil-spec test, the modified test produced elevated strains in the human digital twin. These data, mapped to the cbmTBI criterion, suggest increased injury risk for blunt impacts that cause rotation and translation, rather than just translation alone. Moreover, these data may lead to a rotational performance metric, which is rooted in the biology and pathology of the brain's response to impact and blast, and which should be used to improve next-generation helmet designs.

42 ENGINEERING↗
NASA NTRS2016

On the Efficacy of Isolating Shoulder and Elbow Movements with a Soft, Portable, and Wearable Robotic Device

Treatment intensity has a profound effect on motor recovery following neurological injury. The use of robotics has potential to automate these labor-intensive therapy procedures that are typically performed by physical therapists. Further, the use of wearable robotics offers an aspect of portability that may allow for rehabilitation outside the clinic. The authors have developed a soft, portable, lightweight upper extremity wearable robotic device to provide motor rehabilitation of patients with affected upper limbs due to traumatic brain injury (TBI). A key feature of the device demonstrated in this paper is the isolation of shoulder and elbow movements necessary for effective rehabilitation interventions. Herein is presented a feasibility study with one subject and demonstration of the device's ability to provide safe, comfortable, and controlled upper extremity movements. Moreover, it is shown that by decoupling shoulder and elbow motions, desired isolated joint actuation can be achieved.

Kadivar, Zahra↗
DOE OSTI2021

Brain-implantable multifunctional probe for simultaneous detection of glutamate and GABA neurotransmitters

We report Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA μM -1 cm -2 and maximum sensitivities of 204 ± 15 nA μM -1 cm -2 and 37 ± 7 nA μM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2 , GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Biofidelic Digital Head Model Software

Researchers at Los Alamos have extensive capabilities in biofidelic modeling, simulation and software development for predicting traumatic brain injury (TBI). Since injury-causing experiments cannot be performed on live humans, and head dummies are incapable of predicting brain deformations/strain, our approach uses magnetic resonance imaging (MRI) data for the brain combined with advanced computational methods and substructure constitutive properties to identify harmful accelerations that may develop diffused axonal injury in the brain. The goal is to develop this capability to analyze the effectiveness of personal protective equipment (PPE) such as, helmets and the advanced energy-absorbing materials used in PPE to mitigate brain injury. Los Alamos is seeking a collaborative partner (through a cooperative research and development agreement) to develop this capability toward a potential technology that will have commercial viability.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2024

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Neurosciences & Neurology↗
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↗
NASA NTRS1999

Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved intraoperative neuroprotection.

Review Literature↗
NASA NTRS2010

Signal Processing Methods Monitor Cranial Pressure

Dr. Norden Huang, of Goddard Space Flight Center, invented a set of algorithms (called the Hilbert-Huang Transform, or HHT) for analyzing nonlinear and nonstationary signals that developed into a user-friendly signal processing technology for analyzing time-varying processes. At an auction managed by Ocean Tomo Federal Services LLC, licenses of 10 U.S. patents and 1 domestic patent application related to HHT were sold to DynaDx Corporation, of Mountain View, California. DynaDx is now using the licensed NASA technology for medical diagnosis and prediction of brain blood flow-related problems, such as stroke, dementia, and traumatic brain injury.

Source record↗
NASA NTRS2011

Leveraging Game Consoles for the Delivery of TBI Rehabilitation

Military personnel are at a greater risk for traumatic brain injury (TBI) than the civilian population. In addition, the increase in exposure to explosives, i.e. , improvised explosive devices, in the Afghanistan and Iraq wars, along with more effective body armor, has resulted in far more surviving casualties suffering from TBI than in previous wars. This effort presents the results of a feasibility study and early prototype of a brain injury rehabilitation delivery system (BIRDS). BIRDS is designed to provide medical personnel treating TBI with a capability to prescribe game activities for patients to execute using a commercially available game console, either in a clinical setting or in their homes. These therapeutic activities will contribute to recovery or remediation of the patients' cognitive dysfunctions. Solutions such as this that provide new applications for existing platforms have significant potential to address the growing incidence of TBI today.

Super, Taryn↗
NASA NTRS2014

Introduction

The 2014 SPIE Sensing Technologies for Global Health, Military Medicine and Environmental Monitoring conference embraced a wealth of state-of-the-art information in basic and applied science. This event covered the latest developments in the following areas: Non-invasive Disease Diagnostics for Global Health- This opening series of two consecutive sessions focused on oral biospecimen based rapid assays and point-of-care devices for the detection of pathogens causing infectious diseases, biomarkers for cancer, and analytes for noncommunicable diseases such as diabetes. They also covered presentations on the human proteasome and microbiome with linkage to human diseases and diagnostic approaches. The sessions were built on the past experience and expertise of the National Institutes of Health, National Institutes of Dental and Craniofacial Research. Military Medicine I: Traumatic Brain Injury and PTSD-This assembly covered oral-biomarker based diagnostics for brain damage and TBI as well as prevention and rehabilitation technologies. Neurorehabilitation and noninvasive neuromodulation were also discussed as critical approaches for effective functioning. Military Medicine II: Physiology and Medicine of Extreme Environments and Spaceflight-This scientific segment showcased physiological, pharmacological and diagnostic sensing methodologies during spaceflight per the National Aeronautics and Space Administration as well as military-relevant toxicans and future sensing trends per the Department of Defense. It also included latest technologies to determine hydration status in warfighters, eye surgery using the latest laser technologies, and sensing tools for blood analysis.  Sensing Technologies for Disease Diagnostics and Environmental Monitoring-This closing series of two consecutive sessions provided the venues to learn and discuss more results on the next generation of diagnostic tools and field technologies for diseases, including biomarker detection by digital imaging, multiplex technologies, capillary electrophoresis and molecular platforms serving as labs-on-chips. This conference allowed cross-fertilization of ideas, projects and collaborative work by a multidisciplinary audience of national and international colleagues from the academia, industry and federal government: The National Institutes of Health, National Aeronautics and Space Administration, and the Department of Defense.

Wotring, Virginia E.↗
NASA NTRS2016

Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for elevated ICP can be identified. This may eventually lead to a blood test to diagnose intracranial hypertension.

Zanello, S. B.↗
NASA NTRS2016

Process for Upgrading Cognitive Assessment Capabilities Onboard the International Space Station

MOTIVATION: Spaceflight poses varied and unique risks to the brain and cognitive functioning including radiation exposure, sleep disturbance, fatigue, fluid shifts (increased intracranial pressure), toxin exposure, elevated carbon dioxide, and traumatic brain injury, among others. These potential threats to cognitive functioning are capable of degrading performance and compromising mission success. Furthermore, the threats may increase in severity, and new types of threats may emerge for longer duration exploration missions. This presentation will describe the process used to identify gaps in our current approach, evaluate best practices in cognitive assessment, and transition new cognitive assessment tools to operational use. OVERVIEW: Risks to brain health and performance posed by spaceflight missions require sensitive tools to assess cognitive functioning of astronauts in flight. The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is the automated cognitive assessment tool currently deployed onboard the International Space Station (ISS). WinSCAT provides astronauts and flight surgeons with objective data to monitor neurocognitive functioning. WinSCAT assesses 5 discrete cognitive domains, is sensitive to changes in cognitive functioning, and was designed to be completed in less than 15 minutes. However, WinSCAT does not probe other areas of cognitive functioning that might be important to mission success. Researchers recently have developed batteries that may expand current capabilities, such as increased sensitivity to subtle fluctuations in cognitive functioning. Therefore, we engaged in a systematic process review in order to improve upon our current capabilities and incorporate new advances in cognitive assessment. This process included a literature review on newer measures of neurocognitive assessment, surveys of operational flight surgeons at NASA regarding needs and gaps in our capabilities, and expert panel review of candidate cognitive measures and assessment issues and procedures. SIGNIFICANCE: Our process and the results that flowed from it may be helpful to aeromedical professionals charged with transitioning research findings to operational use. Our specific findings regarding cognitive assessment tools are of significance to professionals who must assess readiness to perform in mission critical situations in environments involving threats to cognition and performance

Picano, J. J.↗
NASA NTRS2019

Noninvasive Breath Analysis Using NASA E-Nose Technology for Health Assessment

Clinical breath analysis is based on the fact that many important metabolites and biomarker molecules are present at detectable levels in exhaled breath, and many of these molecules correlate with human disease or correlate with physiological states that could lead to a decline in health. Presented is a technology that utilizes an array of chemical sensors combined with humidity, temperature and pressure for real time breath analysis to correlate the chemical information in the breath with the state and functioning of different human organs. For example, a marker for pulmonary inflammation processes of the lower respiratory tract, e.g. asthma, is the increase of the nitrogen oxide (NO) concentration in breath. Other volatile biomarkers may correlate with infectious process, metabolic conditions and inflammatory diseases, such as traumatic brain injury (TBI). This technology is also called "electronic nose" (E-Nose) in the sense that the device can mimic human nose to smell odors using a pattern recognition technique to analyze the sensor array data. Breath sampling is non-invasive and can be analyzed in real-time.

Li, Jing↗
NASA NTRSDate not supplied

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗