Neural Stimulation Hardware for the Selective Intrafascicular Modulation of the Vagus Nerve.

The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multi-channel stimulation was performed at different amplitudes. For the first time, a polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions, validating the spatial selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in spatially selective modulation of the vagus nerve. ECAP belonging to alpha and beta fibers could be distinguished during single- and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

Development of a Biosensor for fast point-of-care Blood Analysis of Troponin.

We present the development of novel tetrapolar EIS biosensor for the detect of troponin. Troponin has considerable diagnostic power and provide invaluable prognostic information for risk stratification. of acute coronary syndromes. Clinical Relevance- A feasibility study was undertaken to assess the diagnostic performance of serial cardiac troponin measurements which is excellent as these structural proteins are unique to the heart and thus sensitive and specific of damage to the myocardium. clinical molecular diagnostics and home healthcare. Troponin's biosensors would provide point-of-care and rapid decision making for the early detection of CS. Clinically relevant window of cTnI testing, concentrations from 10pM to 0.1µM were achieved.

Compressive sensing in electrical impedance tomography for breathing monitoring.

OBJECTIVE: Electrical impedance tomography (EIT) is a functional imaging technique in which cross-sectional images of structures are reconstructed based on boundary trans-impedance measurements. Continuous functional thorax monitoring using EIT has been extensively researched. Increasing the number of electrodes, number of planes and frame rate may improve clinical decision making. Thus, a limiting factor in high temporal resolution, 3D and fast EIT is the handling of the volume of raw impedance data produced for transmission and its subsequent storage. Owing to the periodicity (i.e. sparsity in frequency domain) of breathing and other physiological variations that may be reflected in EIT boundary measurements, data dimensionality may be reduced efficiently at the time of sampling using compressed sensing techniques. This way, a fewer number of samples may be taken. APPROACH: Measurements using a 32-electrode, 48-frames-per-second EIT system from 30 neonates were post-processed to simulate random demodulation acquisition method on 2000 frames (each consisting of 544 measurements) for compression ratios (CRs) ranging from 2 to 100. Sparse reconstruction was performed by solving the basis pursuit problem using SPGL1 package. The global impedance data (i.e. sum of all 544 measurements in each frame) was used in the subsequent studies. The signal to noise ratio (SNR) for the entire frequency band (0 Hz-24 Hz) and three local frequency bands were analysed. A breath detection algorithm was applied to traces and the subsequent error-rates were calculated while considering the outcome of the algorithm applied to a down-sampled and linearly interpolated version of the traces as the baseline. MAIN RESULTS: SNR degradation was generally proportional with CR. The mean degradation for 0 Hz-8 Hz (of interest for the target physiological variations) was below ~15 dB for all CRs. The error-rates in the outcome of the breath detection algorithm in the case of decompressed traces were lower than those associated with the corresponding down-sampled traces for CR ⩾ 25, corresponding to sub-Nyquist rate for breathing frequency. For instance, the mean error-rate associated with CR = 50 was ~60% lower than that of the corresponding down-sampled traces. SIGNIFICANCE: To the best of our knowledge, no other study has evaluated the applicability of compressive sensing techniques on raw boundary impedance data in EIT. While further research should be directed at optimising the acquisition and decompression techniques for this application, this contribution serves as the baseline for future efforts.

Torso shape detection to improve lung monitoring.

OBJECTIVE: Newborns with lung immaturity often require continuous monitoring and treatment of their lung ventilation in intensive care units, especially if born preterm. Recent studies indicate that electrical impedance tomography (EIT) is feasible in newborn infants and children, and can quantitatively identify changes in regional lung aeration and ventilation following alterations to respiratory conditions. Information on the patient-specific shape of the torso and its role in minimizing the artefacts in the reconstructed images can improve the accuracy of the clinical parameters obtained from EIT. Currently, only idealized models or those segmented from CT scans are usually adopted. APPROACH: This study presents and compares two methodologies that can detect the patient-specific torso shape by means of wearable devices based on (1) previously reported bend sensor technology, and (2) a novel approach based on the use of accelerometers. MAIN RESULTS: The reconstruction of different phantoms, taking into account anatomical asymmetries and different sizes, are produced for comparison. SIGNIFICANCE: As a result, the accelerometers are more versatile than bend sensors, which cannot be used on bigger cross-sections. The computational study estimates the optimal number of accelerometers required in order to generate an image reconstruction comparable to the use of a CT scan as the forward model. Furthermore, since the patient position is crucial to monitoring lung ventilation, the orientation of the phantoms is automatically detected by the accelerometer-based method.

High-power integrated stimulator output stages with floating discharge over a wide voltage range for nerve stimulation.

Two integrated nerve stimulator circuits are described. Both generate passively charge-balanced biphasic stimulating pulses of 1 to 16 mA with 10-¿s to 1-ms widths from 6- to 24-V supplies for implanted book electrodes. In both circuits, the electrodes are floating during the passive discharge anywhere within the range of the power rails, which may be up to 24 V. The first circuit is used for stimulation only. It uses a floating depletion transistor to enable continuous discharge of the electrodes, except when stimulating, without using power. The second circuit also allows neural signals to be recorded from the same tripole. It uses a modified floating complementary metal-oxide semiconductor (CMOS) discharge switch capable of operating over a range beyond the gate-to-source voltage limits of its transistors. It remains off for long periods using no power while recording. A 0.6-¿m silicon-on-insulator CMOS technology has been used. The measured performance of the circuits has been verified using multiple tripoles in saline.

A case of benign acute childhood myositis associated with influenza A (H1N1) virus infection.

Benign acute childhood myositis (BACM) is a rare transient condition usually occurring at the early convalescent phase of a viral upper respiratory tract illness, normally influenza A, and, more frequently, influenza B infection. It is characterized by acute-onset difficulty in walking as a result of severe bilateral calf pain and by elevated muscle enzymes including creatinine kinase. It is self-limiting because there is rapid full recovery usually within 1 week. We describe the first case of BACM in association with the new pandemic influenza A (H1N1) virus infection in an 11-year-old boy from Cyprus. The child had the typical clinical and laboratory characteristics of this clinical syndrome. Prompt diagnosis of this clinical entity is essential to prevent unnecessary investigations and therapeutic interventions and to reassure the patient and parents of the excellent prognosis.

Epidemiological and clinical characteristics of influenza A(H1N1)v infection in children: The first 45 cases in Cyprus, June - August 2009.

Following the first imported case in a tourist in Cyprus on 2 June 2009, the influenza A(H1N1)v virus has spread on the island affecting mainly young adults and children. We describe here the first 45 cases in children. Fever, cough, rhinorrhoea and sore throat were the most common symptoms of infection. Half of the children had fever for one day or only for a few hours. Five children were hospitalised, and overall their symptoms were mild. Adherence to oseltamivir treatment was very high, with low frequency of gastrointestinal side effects such as nausea and vomiting. Camping places and summer schools played a significant role in spreading the infection among children of school age.

Development of a neonate lung reconstruction algorithm using a wavelet AMG and estimated boundary form.

Objective, non-invasive measures of lung maturity and development, oxygen requirements and lung function, suitable for use in small, unsedated infants, are urgently required to define the nature and severity of persisting lung disease, and to identify risk factors for developing chronic lung problems. Disorders of lung growth, maturation and control of breathing are among the most important problems faced by the neonatologists. At present, no system for continuous monitoring of neonate lung function to reduce the risk of chronic lung disease in infancy in intensive care units exists. We are in the process of developing a new integrated electrical impedance tomography (EIT) system based on wearable technology to integrate measures of the boundary diameter from the boundary form for neonates into the reconstruction algorithm. In principle, this approach could provide a reduction of image artefacts in the reconstructed image associated with incorrect boundary form assumptions. In this paper, we investigate the required accuracy of the boundary form that would be suitable to minimize artefacts in the reconstruction for neonate lung function. The number of data points needed to create the required boundary form is automatically determined using genetic algorithms. The approach presented in this paper is to assist quality of the reconstruction using different approximations to the ideal boundary form. We also investigate the use of a wavelet algebraic multi-grid (WAMG) preconditioner to reduce the reconstruction computation requirements. Results are presented that demonstrate a full 3D model is required to minimize artefact in the reconstructed image and the implementation of a WAMG for EIT.

An Integrated Implantable Stimulator That is Fail-Safe Without Off-Chip Blocking-Capacitors.

We present a neural stimulator chip with an output stage (electrode driving circuit) that is fail-safe under single-fault conditions without the need for off-chip blocking-capacitors. To miniaturize the stimulator output stage two novel techniques are introduced. The first technique is a new current generator circuit reducing to a single step the translation of the digital input bits into the stimulus current, thus minimizing silicon area and power consumption compared to previous works. The current generator uses voltage-controlled resistors implemented by MOS transistors in the deep triode region. The second technique is a new stimulator output stage circuit with blocking-capacitor safety protection using a high-frequency current-switching (HFCS) technique. Unlike conventional stimulator output stage circuits for implantable functional electrical stimulation (FES) systems which require blocking-capacitors in the microfarad range, our proposed approach allows capacitance reduction to the picofarad range, thus the blocking-capacitors can be integrated on-chip. The prototype four-channel neural stimulator chip was fabricated in XFAB's 1-mum silicon-on-insulator CMOS technology and can operate from a power supply between 5-18 V. The stimulus current is generated by active charging and passive discharging. We obtained recordings of action potentials and a strength-duration curve from the sciatic nerve of a frog with the stimulator chip which demonstrate the HFCS technique. The average power consumption for a typical 1-mA 20-Hz single-channel stimulation using a book electrode, is 200 muW from a 6 V power supply. The silicon area occupation is 0.38 mm(2) per channel.

Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented.