Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.

The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1ß and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1ß and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1ß in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1ß and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1ß-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1ß, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve.

Towards maintenance-free biosensors for hundreds of bind/release cycles.

A single aptamer bioreceptor layer was formed using a common streptavidin-biotin immobilization strategy and employed for 100-365 bind/release cycles. Chemically induced aptamer unfolding and release of its bound target was accomplished using alkaline solutions with high salt concentrations or deionized (DI) water. The use of DI water scavenged from the ambient atmosphere represents a first step towards maintenance-free biosensors that do not require the storage of liquid reagents. The aptamer binding affinity was determined by surface plasmon resonance and found to be almost constant over 100-365 bind/release cycles with a variation of less than 5% relative standard deviation. This reversible operation of biosensors based on immobilized aptamers without storage of liquid reagents introduces a conceptually new perspective in biosensing. Such new biosensing capability will be important for distributed sensor networks, sensors in resource-limited settings, and wearable sensor applications.

Efficient Simultaneous Reconstruction of Time-Varying Images and Electrode Contact Impedances in Electrical Impedance Tomography.

OBJECTIVE: In electrical impedance tomography (EIT), we apply patterns of currents on a set of electrodes at the external boundary of an object, measure the resulting potentials at the electrodes, and, given the aggregate dataset, reconstruct the complex conductivity and permittivity within the object. It is possible to maximize sensitivity to internal conductivity changes by simultaneously applying currents and measuring potentials on all electrodes but this approach also maximizes sensitivity to changes in impedance at the interface. METHODS: We have, therefore, developed algorithms to assess contact impedance changes at the interface as well as to efficiently and simultaneously reconstruct internal conductivity/permittivity changes within the body. We use simple linear algebraic manipulations, the generalized singular value decomposition, and a dual-mesh finite-element-based framework to reconstruct images in real time. We are also able to efficiently compute the linearized reconstruction for a wide range of regularization parameters and to compute both the generalized cross-validation parameter as well as the L-curve, objective approaches to determining the optimal regularization parameter, in a similarly efficient manner. RESULTS: Results are shown using data from a normal subject and from a clinical intensive care unit patient, both acquired with the GE GENESIS prototype EIT system, demonstrating significantly reduced boundary artifacts due to electrode drift and motion artifact.

Detection of small bleeds in the brain with electrical impedance tomography.

In this paper, we describe and assess feasibility of instrumentation and algorithms for detecting bleeding due to hemorrhagic strokes and traumatic brain injury using electrical impedance tomography, a novel biomedical diagnostic modality in which the body is probed noninvasively with generally imperceptible alternating currents applied in patterns to a set of electrodes placed in contact with the skin. We focus on the GENESIS instrument developed by GE Global Research and on the achievability of our goal to detect a bleed in the center of the head with a volume of several ml. Our main topic is compensation for the large changes in voltages that tend to occur when the electrodes are in contact with biological media, specifically either human subjects or with vegetable matter proxies which seem to exhibit the same 'drift' phenomenon. We show that these changes in voltages can be modeled by assuming that each electrode is attached to the body via a discrete complex impedance whose value is time-varying and describe how this discrete component value can be estimated and largely compensated-for. We compare this discrete model with changes in contact impedances estimated using the complete electrode model showing that the two models are roughly comparable in their ability to explain the data from a single human subject experiment with electrodes attached to the head. In a simulation study, we demonstrate that it is possible to detect a small bleed in the center of the head even in the case of large changes in electrode impedances, which can be treated as nuisance parameters.

Multi-channel electrical impedance tomography for regional tissue hydration monitoring.

Poor assessment of hydration status during hemodialysis can lead to under- or over-hydration in patients with consequences of increased morbidity and mortality. In current practice, fluid management is largely based on clinical assessments to estimate dry weight (normal hydration body weight). However, hemodialysis patients usually have co-morbidities that can make the signs of fluid status ambiguous. Therefore, achieving normal hydration status remains a major challenge for hemodialysis therapy. Electrical impedance technology has emerged as a promising method for hydration monitoring due to its non-invasive nature, low cost and ease-of-use. Conventional electrical impedance-based hydration monitoring systems employ single-channel current excitation (either 2-electrode or 4-electrode methods) to perturb and extract averaged impedance from bulk tissue and use generalized models from large populations to derive hydration estimates. In the present study, a prototype, single-frequency electrical impedance tomography (EIT) system with simultaneous multi-channel current excitation was used to enable regional hydration change detection. We demonstrated the capability to detect a difference in daily impedance change between left leg and right leg in healthy human subjects, who wore a compression sock only on one leg to reduce daily gravitational fluid accumulation. The impedance difference corresponded well with the difference of lower leg volume change between left leg and right leg measured by volumetry, which on average is ~35 ml, accounting for 0.7% of the lower leg volume. We have demonstrated the feasibility of using multi-channel EIT to extract hydration information in different tissue layers with minimal skin interference. Our simultaneous, multi-channel current excitation approach provides an effective method to separate electrode contact impedance and skin condition artifacts from hydration signals. The prototype system has the potential to be used in clinical settings for helping optimize patient fluid management during hemodialysis as well as for home monitoring of patients with congestive heart failure, chronic kidney disease, diabetes and other diseases with peripheral edema symptoms.