Auditory filter-bank compression improves estimation of signal-to-noise ratio for speech in noise.

Signal-to-noise ratio (SNR) estimation is necessary for many speech processing applications often challenged by nonstationary noise. The authors have previously demonstrated that the variance of spectral entropy (VSE) is a reliable estimate of SNR in nonstationary noise. Based on pre-estimated VSE-SNR relationship functions, the SNR of unseen acoustic environments can be estimated from the measured VSE. This study predicts that introducing a compressive function based on cochlear processing will increase the stability of the pre-estimated VSE-SNR relationship functions. This study demonstrates that calculating the VSE based on a nonlinear filter-bank, simulating cochlear compression, reduces the VSE-based SNR estimation errors. VSE-SNR relationship functions were estimated using speech tokens presented in babble noise comprised of different numbers of speakers. Results showed that the coefficient of determination (R2) of the estimated VSE-SNR relationship functions have absolute percentage improvements of over 26% when using a filter-bank with a compressive function, compared to when using a linear filter-bank without compression. In 2-talker babble noise, the estimation accuracy is more than 3 dB better than other published methods.

Towards a System for Tracking Drug Delivery Using Frequency Excited Gold Nanoparticles.

Nanoparticle-based drugs are rapidly evolving to treat different conditions and have considerable potential. A new system based on the combination of electrical impedance tomography (EIT) imaging and a power amplifier with a RF coil has been developed to study the effect of gold nanoparticles (AuNPs) when excited in the MHz frequency range. We show that samples including AuNPs have a temperature increase of 1-1.5 °C due to the presence of RF excitation at 13.56 MHz which provides a higher rate of change for solutions without AuNPs. They also show more than a 50% increase in conductivity in difference imaging as the result of this excitation. The change for samples without AuNPs is 40%.

Analog Integrated Current Drivers for Bioimpedance Applications: A Review.

An important component in bioimpedance measurements is the current driver, which can operate over a wide range of impedance and frequency. This paper provides a review of integrated circuit analog current drivers which have been developed in the last 10 years. Important features for current drivers are high output impedance, low phase delay, and low harmonic distortion. In this paper, the analog current drivers are grouped into two categories based on open loop or closed loop designs. The characteristics of each design are identified.

Effect of auditory efferent time-constant duration on speech recognition in noise.

The human auditory efferent system may play a role in improving speech-in-noise recognition with an associated range of time constants. Computational auditory models with efferent-inspired feedback demonstrate improved speech-in-noise recognition with long efferent time constants (2000 ms). This study used a similar model plus an Automatic Speech Recognition (ASR) system to investigate the role of shorter time constants. ASR speech recognition in noise improved with efferent feedback (compared to no-efferent feedback) for both short and long efferent time constants. For some signal-to-noise ratios, speech recognition in noise improved as efferent time constants were increased from 118 to 2000 ms.

Optimized Lateral Flow Immunoassay Reader for the Detection of Infectious Diseases in Developing Countries.

Detection and control of infectious diseases is a major problem, especially in developing countries. Lateral flow immunoassays can be used with great success for the detection of infectious diseases. However, for the quantification of their results an electronic reader is required. This paper presents an optimized handheld electronic reader for developing countries. It features a potentially low-cost, low-power, battery-operated device with no added optical accessories. The operation of this proof of concept device is based on measuring the reflected light from the lateral flow immunoassay and translating it into the concentration of the specific analyte of interest. Characterization of the surface of the lateral flow immunoassay has been performed in order to accurately model its response to the incident light. Ray trace simulations have been performed to optimize the system and achieve maximum sensitivity by placing all the components in optimum positions. A microcontroller enables all the signal processing to be performed on the device and a Bluetooth module allows transmission of the results wirelessly to a mobile phone app. Its performance has been validated using lateral flow immunoassays with influenza A nucleoprotein in the concentration range of 0.5 ng/mL to 200 ng/mL.

Wideband Fully-Programmable Dual-Mode CMOS Analogue Front-End for Electrical Impedance Spectroscopy.

This paper presents a multi-channel dual-mode CMOS analogue front-end (AFE) for electrochemical and bioimpedance analysis. Current-mode and voltage-mode readouts, integrated on the same chip, can provide an adaptable platform to correlate single-cell biosensor studies with large-scale tissue or organ analysis for real-time cancer detection, imaging and characterization. The chip, implemented in a 180-nm CMOS technology, combines two current-readout (CR) channels and four voltage-readout (VR) channels suitable for both bipolar and tetrapolar electrical impedance spectroscopy (EIS) analysis. Each VR channel occupies an area of 0.48 mm 2 , is capable of an operational bandwidth of 8 MHz and a linear gain in the range between -6 dB and 42 dB. The gain of the CR channel can be set to 10 kΩ, 50 kΩ or 100 kΩ and is capable of 80-dB dynamic range, with a very linear response for input currents between 10 nA and 100 µ A. Each CR channel occupies an area of 0.21 mm 2 . The chip consumes between 530 µ A and 690 µ A per channel and operates from a 1.8-V supply. The chip was used to measure the impedance of capacitive interdigitated electrodes in saline solution. Measurements show close matching with results obtained using a commercial impedance analyser. The chip will be part of a fully flexible and configurable fully-integrated dual-mode EIS system for impedance sensors and bioimpedance analysis.

Frequency Splitting Analysis and Compensation Method for Inductive Wireless Powering of Implantable Biosensors.

Inductive powering for implanted medical devices, such as implantable biosensors, is a safe and effective technique that allows power to be delivered to implants wirelessly, avoiding the use of transcutaneous wires or implanted batteries. Wireless powering is very sensitive to a number of link parameters, including coil distance, alignment, shape, and load conditions. The optimum drive frequency of an inductive link varies depending on the coil spacing and load. This paper presents an optimum frequency tracking (OFT) method, in which an inductive power link is driven at a frequency that is maintained at an optimum value to ensure that the link is working at resonance, and the output voltage is maximised. The method is shown to provide significant improvements in maintained secondary voltage and system efficiency for a range of loads when the link is overcoupled. The OFT method does not require the use of variable capacitors or inductors. When tested at frequencies around a nominal frequency of 5 MHz, the OFT method provides up to a twofold efficiency improvement compared to a fixed frequency drive. The system can be readily interfaced with passive implants or implantable biosensors, and lends itself to interfacing with designs such as distributed implanted sensor networks, where each implant is operating at a different frequency.

Flexible active electrode arrays with ASICs that fit inside the rat's spinal canal.

Epidural spinal cord electrical stimulation (ESCS) has been used as a means to facilitate locomotor recovery in spinal cord injured humans. Electrode arrays, instead of conventional pairs of electrodes, are necessary to investigate the effect of ESCS at different sites. These usually require a large number of implanted wires, which could lead to infections. This paper presents the design, fabrication and evaluation of a novel flexible active array for ESCS in rats. Three small (1.7 mm(2)) and thin (100 µm) application specific integrated circuits (ASICs) are embedded in the polydimethylsiloxane-based implant. This arrangement limits the number of communication tracks to three, while ensuring maximum testing versatility by providing independent access to all 12 electrodes in any configuration. Laser-patterned platinum-iridium foil forms the implant's conductive tracks and electrodes. Double rivet bonds were employed for the dice microassembly. The active electrode array can deliver current pulses (up to 1 mA, 100 pulses per second) and supports interleaved stimulation with independent control of the stimulus parameters for each pulse. The stimulation timing and pulse duration are very versatile. The array was electrically characterized through impedance spectroscopy and voltage transient recordings. A prototype was tested for long term mechanical reliability when subjected to continuous bending. The results revealed no track or bond failure. To the best of the authors' knowledge, this is the first time that flexible active electrode arrays with embedded electronics suitable for implantation inside the rat's spinal canal have been proposed, developed and tested in vitro.

A CMOS smart temperature and humidity sensor with combined readout.

A fully-integrated complementary metal-oxide semiconductor (CMOS) sensor for combined temperature and humidity measurements is presented. The main purpose of the device is to monitor the hermeticity of micro-packages for implanted integrated circuits and to ensure their safe operation by monitoring the operating temperature and humidity on-chip. The smart sensor has two modes of operation, in which either the temperature or humidity is converted into a digital code representing a frequency ratio between two oscillators. This ratio is determined by the ratios of the timing capacitances and bias currents in both oscillators. The reference oscillator is biased by a current whose temperature dependency is complementary to the proportional to absolute temperature (PTAT) current. For the temperature measurement, this results in an exceptional normalized sensitivity of about 0.77%/°C at the accepted expense of reduced linearity. The humidity sensor is a capacitor, whose value varies linearly with relative humidity (RH) with a normalized sensitivity of 0.055%/% RH. For comparison, two versions of the humidity sensor with an area of either 0.2 mm2 or 1.2 mm2 were fabricated in a commercial 0.18 µm CMOS process. The on-chip readout electronics operate from a 5 V power supply and consume a current of approximately 85 µA.

Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review.

Interfaces with peripheral nerves have been widely developed to enable bioelectronic control of neural activity. Peripheral nerve neuromodulation shows great potential in addressing motor dysfunctions, neurological disorders, and psychiatric conditions. The integration of high-density neural electrodes with stimulation and recording circuits poses a challenge in the design of neural interfaces. Recent advances in active electrode strategies have achieved improved reliability and performance by implementing in-situ control, stimulation, and recording of neural fibers. This paper presents an overview of state-of-the-art neural interface systems that comprise a range of neural electrodes, neurostimulators, and bio-amplifier circuits, with a special focus on interfaces for the peripheral nerves. A discussion on the efficacy of active electrode systems and recommendations for future directions conclude this paper.

An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of amyotrophic lateral sclerosis.

Breakdown of neuromuscular junctions (NMJs) is an early pathological hallmark of amyotrophic lateral sclerosis (ALS) that blocks neuromuscular transmission, leading to muscle weakness, paralysis and, ultimately, premature death. Currently, no therapies exist that can prevent progressive motor neuron degeneration, muscle denervation, or paralysis in ALS. Here, we report important advances in the development of an optogenetic, neural replacement strategy that can effectively restore innervation of severely affected skeletal muscles in the aggressive SOD1G93A mouse model of ALS, thus providing an interface to selectively control the function of targeted muscles using optical stimulation. We also identify a specific approach to confer complete survival of allogeneic replacement motor neurons. Furthermore, we demonstrate that an optical stimulation training paradigm can prevent atrophy of reinnervated muscle fibers and results in a tenfold increase in optically evoked contractile force. Together, these advances pave the way for an assistive therapy that could benefit all ALS patients.

A multi-channel stimulator with an active electrode array implant for vagal-cardiac neuromodulation studies.

BACKGROUND: Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. METHODS: This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. RESULTS: The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. CONCLUSIONS: The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

Vaccination delays Maedi-Visna lentivirus infection in a naturally-infected sheep flock.

BACKGROUND: The Maedi-Visna (MV) lentivirus causes two slowly progressive eventually fatal diseases of sheep, Maedi, a progressive interstitial pneumonia, and Visna, a progressive demyelinating disease of the central nervous system. Other lentiviruses also cause fatal slow infections in their natural hosts, e.g. the HIV virus in humans. Results of experimental vaccination against any lentivirus where vaccinees are challenged by natural routes, may therefore be of general interest. From 1991-1998 experiments with formalin-inactivated whole Maedi-Visna virus vaccine were carried out in the Department of Microbiology at the University of Iceland. Western Blot tests showed good immune response to all major proteins of the virus. When aluminium hydroxide was added to the vaccine all vaccinees developed neutralizing antibodies to the vaccine strain at titers 1/8 - 1/256. After housing 5 twin pairs, one twin in each pair vaccinated, the other unvaccinated, with infected sheep for 4 years, all the unvaccinated twins became infected, but only 2 of their vaccinated siblings as confirmed by virus cultivation experiments on tissues from their lungs spleens lymph nodes and choroid plexuses. RESULTS: One twin in each of 40 female twin pairs, born into a Maedi-Visna-infected sheep flock and kept under natural farming conditions in Cyprus, was vaccinated at birth, 3 weeks and 3 months, with formalin-inactivated whole Maedi-Visna lentivirus vaccine adjuvanted with aluminium hydroxide. 17 mothers of the twins were seronegative, 13 seroconverting and 10 had old infection. Of 17 vaccinees born to seronegative mothers 9 were uninfected at 28 months, but only 2 of their unvaccinated siblings. Of 13 unvaccinated twins born to seroconverting mothers, 12 caught infection during their first 10 weeks, but only 4 of their vaccinated siblings. Vaccination had no effects on 10 vaccinees born to mothers with long-standing Maedi-Visna infections and broad andibody response at birth of their lambs. CONCLUSION: Compared with their unvaccinated siblings, natural infection was delayed in significant number of vaccinated twins born by seronegative and seroconverting mothers and vaccinated at birth, 3 weeks and 3 months with formalin inactivated whole MV vaccine adjuvanted with aluminium hydroxide. Maternal antibodies interfered with vaccination so early in life if the mother had old infection.

Generation of Anatomically Inspired Human Airway Tree Using Electrical Impedance Tomography: A Method to Estimate Regional Lung Filling Characteristics.

The purpose of lung recruitment is to improve and optimize the air exchange flow in the lungs by adjusting the respiratory settings during mechanical ventilation. Electrical impedance tomography (EIT) is a monitoring tool that permits measurement of regional pulmonary filling characteristics or filling index (FI) during ventilation. The conventional EIT system has limitations which compromise the accuracy of the FI. This paper proposes a novel and automated methodology for accurate FI estimation based on EIT images of recruitable regional collapse and hyperdistension during incremental positive end-expiratory pressure. It identifies details of the airway tree (AT) to generate a correction factor to the FIs providing an accurate measurement. Multi-scale image enhancement followed by identification of the AT skeleton with a robust and self-exploratory tracing algorithm is used to automatically estimate the FI. AT tracing was validated using phantom data on a ground-truth lung. Based on generated phantom EIT images, including an established reference, the proposed method results in more accurate FI estimation of 65% in all quadrants compared with the current state-of-the-art. Measured regional filling characteristics were also examined by comparing regional and global impedance variations in clinically recorded data from ten different subjects. Clinical tests on filling characteristics based on extraction of the AT from the resolution enhanced EIT images indicated a more accurate result compared with the standard EIT images.

Efficient Approximation of Action Potentials with High-Order Shape Preservation in Unsupervised Spike Sorting.

This paper presents a novel approximation unit added to the conventional spike processing chain which provides an appreciable reduction of complexity of the high-hardware cost feature extractors. The use of the Taylor polynomial is proposed and modelled employing its cascaded derivatives to non-uniformly capture the essential samples in each spike for reliable feature extraction and sorting. Inclusion of the approximation unit can provide 3X compression (i.e. from 66 to 22 samples) to the spike waveforms while preserving their shapes. Detailed spike waveform sequences based on in-vivo measurements have been generated using a customized neural simulator for performance assessment of the approximation unit tested on six published feature extractors. For noise levels σN between 0.05 and 0.3 and groups of 3 spikes in each channel, all the feature extractors provide almost same sorting performance before and after approximation. The overall implementation cost when including the approximation unit and feature extraction shows a large reduction (i.e. up to 8.7X) in the hardware costly and more accurate feature extractors, offering a substantial improvement in feature extraction design.

Insertion Guidance Based on Impedance Measurements of a Cochlear Electrode Array.

The cochlear implantable neuromodulator provides substantial auditory perception to those with severe or profound impaired hearing. Correct electrode array positioning in the cochlea is one of the important factors for quality hearing, and misplacement may lead to additional injury to the cochlea. Visual inspection of the progress of electrode insertion is limited and mainly relies on the surgeon's tactile skills, and there is a need to detect in real-time the electrode array position in the cochlea during insertion. The available clinical measurement presently provides very limited information. Impedance measurement may be used to assist with the insertion of the electrode array. Using computational modeling of the cochlea, and its local tissue layers merging with the associated neuromodulator electrode array parameters, the impedance variations at different insertion depths and the proximities to the cochlea walls have been analyzed. In this study, an anatomical computational model of the temporal region of a patient is used to derive the relationship between impedance variations and the electrode proximity to the cochlea wall and electrode insertion depth. The aim was to examine whether the use of electrode impedance variations can be an effective marker of electrode proximity and electrode insertion depth. The proposed anatomical model simulates the quasi-static electrode impedance variations at different selected points but at considerable computation cost. A much less computationally intensive geometric model (~1/30) provided comparative impedance measurements with differences of <2%. Both use finite element analysis over the entire cross-section area of the scala tympani. It is shown that the magnitude of the impedance varies with both electrode insertion depth and electrode proximity to the adjacent anatomical layers (e.g., cochlea wall). In particular, there is a 1,400% increase when the electrode array is moved very close to the cochlea wall. This may help the surgeon to find the optimal electrode position within the scala tympani by observation of such impedance characteristics. The misplacement of the electrode array within the scala tympani may be eliminated by using the impedance variation metric during electrode array insertion if the results are validated with an experimental study.

High Frame Rate Electrical Impedance Tomography System for Monitoring of Regional Lung Ventilation.

This paper describes the development of a compact high frame rate passive electrical impedance tomography system. The injected current amplitude and frequency can be adjusted to fit any EIT application. Measured results show that the system is capable of high frame rate of 89 fps and has power consumption of 1.7 W. It has automatic gain control that reduces noise and improves the quality of the measured EIT image. A comparison is made with other EIT systems to show the potential of the developed system. Clinical Relevance- The developed EIT system has application in the clinical assessment of neonatal and SARS-Co V-2 patients. In these applications there is an urgent need for a low cost bedside non-invasive imaging system to continuously monitor dynamic changes in regional lung ventilation.

Multimodal Diagnosis for Pulmonary Embolism from EHR Data and CT Images.

Pulmonary Embolism (PE) is a severe medical condition that can pose a significant risk to life. Traditional deep learning methods for PE diagnosis are based on Computed Tomography (CT) images and do not consider the patient's clinical context. To make full use of patient's clinical information, this article presents a multimodal fusion model ingesting Electronic Health Record (EHR) data and CT images for PE diagnosis. The proposed model is based on multilayer perception and convolutional neural networks. To remove the invalid information in the EHR data, the multidimensional scaling algorithm is performed for feature dimension reduction. The EHR data and CT images of 600 patients are used for experiments. The experiment results show that the proposed models outperform existing methods and the multimodal fusion model shows better performance than the single-input model.

Cross-sectional chest circumference and shape development in infants.

OBJECTIVE: This study investigates the development of the thoracic cross-section at the nipple line level during the early stages of life. Unlike the descriptive awareness regarding chest development course, there exist no quantitative references concerning shape, circumference and possible dependencies to age, gender or body weight. The proposed mathematical relations are expected to help create guidelines for more realistic modelling and potential detection of abnormalities. One potential application is lung electrical impedance tomography (EIT) monitoring where accurate chest models are crucial in both extracting reliable parameters for regional ventilation function and design of EIT belts. Despite their importance, such reference data is not readily available for the younger age range due to insufficient data amid the regulations of neonatal imaging. RESULTS: Chest circumference shows the highest correlation to body weight following the relation [Formula: see text] where x is the body weight in grams and f(x) is the chest circumference in cm at the nipple line level. No statistically significant difference in chest circumference between genders was detected. However, the shape indicated signs of both age and gender dependencies with on average boys developing a more rectangular shape than girls from the age of 1 years and 9 months.

A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies.

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method.