Nonresonant Transmission Line Probe for Sensitive Interferometric Electron Spin Resonance Detection.

Electron spin resonance (ESR) spectroscopy measures paramagnetic free radicals, or electron spins, in a variety of biological, chemical, and physical systems. Detection of diverse paramagnetic species is important in applications ranging from quantum computation to biomedical research. Countless efforts have been made to improve the sensitivity of ESR detection. However, the improvement comes at the cost of experimental accessibility. Thus, most ESR spectrometers are limited to specific sample geometries and compositions. Here, we present a nonresonant transmission line ESR probe (microstrip geometry) that effectively couples high frequency microwave magnetic field into a wide range of sample geometries and compositions. The nonresonant transmission line probe maintains detection sensitivity while increasing availability to a wider range of applications. The high frequency magnetic field homogeneity is greatly increased by positioning the sample between the microstrip signal line and the ground plane. Sample interfacing occurs via a universal sample holder which is compatible with both solid and liquid samples. The unavoidable loss in sensitivity due to the nonresonant nature of the transmission line probe (low Q) is recuperated by using a highly sensitive microwave interferometer-based detection circuit. The combination of our sensitive interferometer and nonresonant transmission line provides similar sensitivity to a commercially available ESR spectrometer equipped with a high-Q resonator. The nonresonant probe allows for transmission, reflection, or dual-mode detection (transmission and reflection), where the dual-mode results in a √2 signal enhancement.

Cerebellum, Basal Ganglia, and Cortex Mediate Performance of an Aerial Pursuit Task.

The affordance competition hypothesis is an ethologically inspired theory from cognitive neuroscience that provides an integrative neural account of continuous, real-time behavior, and will likely become increasingly relevant to the growing field of neuroergonomics. In the spirit of neuroergonomics in aviation, we designed a three-dimensional, first-person, continuous, and real-time fMRI task during which human subjects maneuvered a simulated airplane in pursuit of a target airplane along constantly changing headings. We introduce a pseudo-event-related, parametric fMRI analysis approach to begin testing the affordance competition hypothesis in neuroergonomic contexts, and attempt to identify regions of the brain that exhibit a linear metabolic relationship with the continuous variables of task performance and distance-from-target. In line with the affordance competition hypothesis, our results implicate the cooperation of the cerebellum, basal ganglia, and cortex in such a task, with greater involvement of the basal ganglia during good performance, and greater involvement of cortex and cerebellum during poor performance and when distance-from-target closes. We briefly review the somatic marker and dysmetria of thought hypotheses, in addition to the affordance competition hypothesis, to speculate on the intricacies of the cooperation of these brain regions in a task such as ours. In doing so, we demonstrate how the affordance competition hypothesis and other cognitive neuroscience theories are ready for testing in continuous, real-time tasks such as ours, and in other neuroergonomic settings more generally.

Resting State Functional Connectivity MRI among Spectral MEG Current Sources in Children on the Autism Spectrum.

Social and communicative impairments are among the core symptoms of autism spectrum disorders (ASD), and a great deal of evidence supports the notion that these impairments are associated with aberrant functioning and connectivity of various cortical networks. The present study explored the links between sources of MEG amplitude in various frequency bands and functional connectivity MRI in the resting state. The goal of combining these modalities was to use sources of neural oscillatory activity, measured with MEG, as functionally relevant seed regions for a more traditional pairwise fMRI connectivity analysis. We performed a seed-based connectivity analysis on resting state fMRI data, using seed regions derived from frequency-specific amplitude sources in resting state MEG data in the same nine subjects with ASD (10-17 years of age). We then compared fMRI connectivity among these MEG-source-derived regions between participants with autism and typically developing, age-matched controls. We used a source modeling technique designed for MEG data to detect significant amplitude sources in six frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-60 Hz), and high gamma (60-120 Hz). MEG-derived source maps for each participant were co-registered in standard MNI space, and group-level source maps were obtained for each frequency. For each frequency band, the 10 largest clusters resulting from these t-tests were used as regions of interest (ROIs) for the fMRI functional connectivity analysis. Pairwise BOLD signal correlations were obtained between each pair of these ROIs for each frequency band. Each pairwise correlation was compared between the ASD and TD groups using t-tests. We also constrained these pairwise correlations to known network structures, resulting in a follow-up set of correlation matrices specific to each network we considered. Frequency-specific MEG sources had distinct patterns of fMRI resting state functional connectivity in the ASD group, but perhaps the most significant was a finding of hypoconnectivity between many sources of low and high gamma activity. These novel findings suggest that in ASD there are differences in functionally defined networks as shown in previous fMRI studies, as well as between sets of regions defined by magnetoencephalographic neural oscillatory activity.

A critical assessment of biodosimetry methods for large-scale incidents.

Recognition is growing regarding the possibility that terrorism or large-scale accidents could result in potential radiation exposure of hundreds of thousands of people and that the present guidelines for evaluation after such an event are seriously deficient. Therefore, there is a great and urgent need for after-the-fact biodosimetric methods to estimate radiation dose. To accomplish this goal, the dose estimates must be at the individual level, timely, accurate, and plausibly obtained in large-scale disasters. This paper evaluates current biodosimetry methods, focusing on their strengths and weaknesses in estimating human radiation exposure in large-scale disasters at three stages. First, the authors evaluate biodosimetry's ability to determine which individuals did not receive a significant exposure so they can be removed from the acute response system. Second, biodosimetry's capacity to classify those initially assessed as needing further evaluation into treatment-level categories is assessed. Third, we review biodosimetry's ability to guide treatment, both short- and long-term, is reviewed. The authors compare biodosimetric methods that are based on physical vs. biological parameters and evaluate the features of current dosimeters (capacity, speed and ease of getting information, and accuracy) to determine which are most useful in meeting patients' needs at each of the different stages. Results indicate that the biodosimetry methods differ in their applicability to the three different stages, and that combining physical and biological techniques may sometimes be most effective. In conclusion, biodosimetry techniques have different properties, and knowledge of their properties for meeting the different needs for different stages will result in their most effective use in a nuclear disaster mass-casualty event.

The view from the trenches: part 1-emergency medical response plans and the need for EPR screening.

Few natural disasters or intentional acts of war or terrorism have the potential for such severe impact upon a population and infrastructure as the intentional detonation of a nuclear device within a major U.S. city. In stark contrast to other disasters or even a "dirty bomb," hundreds of thousands will be affected and potentially exposed to a clinically significant dose of ionizing radiation. This will result in immediate deaths and injuries and subsequently the development of Acute Radiation Syndrome (ARS). Additionally, millions more who are unlikely to develop ARS will seek medical evaluation and treatment, overwhelming the capacity of an already compromised medical system. In this paper, the authors propose that in vivo electron paramagnetic resonance (EPR) dosimetry be utilized to screen large numbers of potentially exposed victims, and that this screening process be incorporated into the medical-surge framework that is currently being implemented across the nation for other catastrophic public health emergencies. The National Incident Management System (NIMS), the National Response Framework (NRF), the Target Capabilities List (TCL), Homeland Security Presidential Directives (HSPD), as well as additional guidance from multiple federal agencies provide a solid framework for this response. The effective screening of potentially-exposed victims directly following a nuclear attack could decrease the number of patients seeking immediate medical care by greater than 90%.

Proposed triage categories for large-scale radiation incidents using high-accuracy biodosimetry methods.

A catastrophic event such as a nuclear device detonation in a major U.S. city would cause a mass casualty with millions affected. Such a disaster would require screening to accurately and effectively identify patients likely to develop acute radiation syndrome (ARS). A primary function of such screening is to sort the unaffected, or worried-well, from those patients who will truly become symptomatic. This paper reviews the current capability of high-accuracy biodosimetry methods as screening tools for populations and reviews the current triage and medical guidelines for diagnosing and managing ARS. This paper proposes that current triage categories, which broadly categorize patients by likelihood of survival based on current symptoms, be replaced with new triage categories that use high-accuracy biodosimetry methods. Using accurate whole-body exposure dose assessment to predict ARS symptoms and subsyndromes, clinical decision-makers can designate the appropriate care setting, initiate treatment and therapies, and best allocate limited clinical resources, facilitating mass-casualty care following a nuclear disaster.

The view from the trenches: part 2-technical considerations for EPR screening.

There is growing awareness of the need for methodologies that can be used retrospectively to provide the biodosimetry needed to carry out screening and triage immediately after an event in which large numbers of people have potentially received clinically significant doses of ionizing radiation. The general approach to developing such methodologies has been a technology centric one, often ignoring the system integrations considerations that are key to their effective use. In this study an integrative approach for the evaluation and development of a physical biodosimetry technology was applied based on in vivo electron paramagnetic resonance (EPR) dosimetry. The EPR measurements are based on physical changes in tissues whose magnitudes are not affected by the factors that can confound biologically-based assessments. In this study the use of a pilot simulation exercise to evaluate an experimental EPR system and gather stakeholders' feedback early on in the development process is described. The exercise involved: ten non-irradiated participants, representatives from a local fire department; Department of Homeland Security certified exercise evaluators, EPR experts, physicians; and a human factors engineer. Stakeholders were in agreement that the EPR technology in its current state of development could be deployed for the screening of mass casualties. Furthermore, stakeholders' recommendations will be prioritized and incorporated in future developments of the EPR technique. While the results of this exercise were aimed specifically at providing feedback for the development of EPR dosimetry for screening mass casualties, the methods and lessons learned are likely to be applicable to other biodosimetric methods.