All-printed stretchable corneal sensor on soft contact lenses for noninvasive and painless ocular electrodiagnosis.

Electroretinogram examinations serve as routine clinical procedures in ophthalmology for the diagnosis and management of many ocular diseases. However, the rigid form factor of current corneal sensors produces a mismatch with the soft, curvilinear, and exceptionally sensitive human cornea, which typically requires the use of topical anesthesia and a speculum for pain management and safety. Here we report a design of an all-printed stretchable corneal sensor built on commercially-available disposable soft contact lenses that can intimately and non-invasively interface with the corneal surface of human eyes. The corneal sensor is integrated with soft contact lenses via an electrochemical anchoring mechanism in a seamless manner that ensures its mechanical and chemical reliability. Thus, the resulting device enables the high-fidelity recording of full-field electroretinogram signals in human eyes without the need of topical anesthesia or a speculum. The device, superior to clinical standards in terms of signal quality and comfortability, is expected to address unmet clinical needs in the field of ocular electrodiagnosis.

Noninvasive measurement of sensory action currents in the cervical cord by magnetospinography.

OBJECTIVE: To obtain magnetic recordings of electrical activities in the cervical cord and visualize sensory action currents of the dorsal column, intervertebral foramen, and dorsal horn. METHODS: Neuromagnetic fields were measured at the neck surface upon median nerve stimulation at the wrist using a magnetospinography system with high-sensitivity superconducting quantum interference device sensors. Somatosensory evoked potentials (SEPs) were also recorded. Evoked electrical currents were reconstructed by recursive null-steering beamformer and superimposed on cervical X-ray images. RESULTS: Estimated electrical currents perpendicular to the cervical cord ascended sequentially. Their peak latency at C5 and N11 peak latency of SEP were well-correlated in all 16 participants (r = 0.94, p < 0.0001). Trailing axonal currents in the intervertebral foramens were estimated in 10 participants. Estimated dorsal-ventral electrical currents were obtained within the spinal canal at C5. Current density peak latency significantly correlated with cervical N13-P13 peak latency of SEPs in 13 participants (r = 0.97, p < 0.0001). CONCLUSIONS: Magnetospinography shows excellent spatial and temporal resolution after median nerve stimulation and can identify the spinal root entry level, calculate the dorsal column conduction velocity, and analyze segmental dorsal horn activity. SIGNIFICANCE: This approach is useful for functional electrophysiological diagnosis of somatosensory pathways.

In vivo muscle conduction study of the tongue using a multi-electrode tongue depressor.

OBJECTIVE: To test a novel technology for assessment of the volume conduction properties (VCPs) of the tongue. These properties are electrophysiological data that might reflect alterations in patients with tongue involvement. METHODS: Seven healthy individuals were self-measured. The depressor was placed on the surface of the anterior tongue. Directional differences of VCPs were determined with standard descriptive statistics. RESULTS: Conductivity in longitudinal direction was larger than in transverse direction at 16 (p < 0.05), 32 (p < 0.05), 64 (p < 0.01), and 128 kHz (p < 0.01). No differences were found in relative permittivity. The intraclass correlation was 0.778 and 0.771, respectively. CONCLUSIONS: Our technology provides, for the first time, VCPs of the healthy human tongue. SIGNIFICANCE: Tongue VCPs are standard electrophysiological, quantitative and objective data reflecting ionic content and membrane integrity which could find value for diagnostic purposes and treatment monitoring.

Head phantoms for bioelectromagnetic applications: a material study.

BACKGROUND: Assessments of source reconstruction procedures in electroencephalography and computations of transcranial electrical stimulation profiles require verification and validation with the help of ground truth configurations as implemented by physical head phantoms. For these phantoms, synthetic materials are needed, which are mechanically and electrochemically stable and possess conductivity values similar to the modeled human head tissues. Three-compartment head models comprise a scalp layer with a conductivity range of 0.137 S/m to 2.1 S/m, a skull layer with conductivity values between 0.066 S/m and 0.00275 S/m, and an intracranial volume with an often-used average conductivity value of 0.33 S/m. To establish a realistically shaped physical head phantom with a well-defined volume conduction configuration, we here characterize the electrical conductivity of synthetic materials for modeling head compartments. We analyzed agarose hydrogel, gypsum, and sodium chloride (NaCl) solution as surrogate materials for scalp, skull, and intracranial volume. We measured the impedance of all materials when immersed in NaCl solution using a four-electrode setup. The measured impedance values were used to calculate the electrical conductivity values of each material. Further, the conductivities in the longitudinal and transverse directions of reed sticks immersed in NaCl solution were measured to test their suitability for mimicking the anisotropic conductivity of white matter tracts. RESULTS: We obtained conductivities of 0.314 S/m, 0.30 S/m, 0.311 S/m (2%, 3%, 4% agarose), 0.0425 S/m and 0.0017 S/m (gypsum with and without NaCl in the compound), and 0.332 S/m (0.17% NaCl solution). These values are within the range of the conductivity values used for EEG and TES modeling. The reed sticks showed anisotropic conductivity with a ratio of 1:2.8. CONCLUSION: We conclude that agarose, gypsum, and NaCl solution can serve as stable representations of the three main conductivity compartments of the head, i.e., scalp, skull, and intracranial volume. An anisotropic conductivity structure such as a fiber track in white matter can be modeled using tailored reed sticks inside a volume conductor.

Use of MarginProbe as an adjunct to standard operating procedure does not significantly reduce re-excision rates in breast conserving surgery.

PURPOSE: A positive margin after breast conserving surgery has consistently been shown to be a significant predictor for ipsilateral breast tumor recurrence. Currently, there is no standard for intraoperative margin assessment during lumpectomy, and up to 20% of cases result in positive margins. MarginProbe is a device that provides real-time evaluation of lumpectomy margins during surgery. The aim of this study was to evaluate the impact of MarginProbe as an adjunct to standard operating procedure (SOP). METHODS: Patients diagnosed with breast cancer scheduled for breast conserving surgery were consented for intraoperative use of MarginProbe. Shaved margins were excised based on margin assessment using the surgeon's SOP which included specimen radiography and gross pathologic examination, and feedback from the device. The primary endpoint was re-excision rate. Secondary endpoints included sensitivity, specificity, false-positive and negative rates. RESULTS: Of the 60 breast cancers, initial histologically close/positive margins were identified in 18 patients (30%). The re-excision rate in the overall cohort was 6.6%, compared to a historical re-excision rate of 8.6% (p < 0.01). Based on 360 measurement sites, MarginProbe demonstrated a sensitivity of 67% and specificity of 60%, with a positive predictive value of 16%, and of negative predictive value of 94%, which was similar to the accuracy of SOP. CONCLUSIONS: MarginProbe performs equally as well as specimen radiography and gross pathologic examination. In this setting where the baseline re-excision rate was low, the use of MarginProbe as an adjunct to SOP resulted in a small 2% absolute reduction in re-excision rate.

Intra and inter-raters reliability and agreement of stimulus electrodiagnostic tests with two different electrodes in sedated critically-ill patients.

Objective: The aim of the present study was to verify the intra- and inter-rater reliability and agreement of the stimulus electrodiagnostic test (SET) measurements obtained by pen and square electrodes in the vastus lateralis and tibialis anterior muscles. Design: An intra- and inter-rater reliability and agreement study was performed for the SET by two independent raters. Two different sizes of cathode electrodes (1 cm2 and 25 cm2) and two muscles were assessed (tibialis anterior and vastus lateralis). Results: Chronaxie did not change according to the different electrodes. A high intra-rater reliability (0.72 ≤ r ≤ 0.88) was detected independently of the electrode and muscle assessed. Moreover, moderate and almost perfect agreements (0.51 ≤ Kappa ≤ 1.00) were detected on intra-rater assessment. Similar correlations (0.74 ≤ r ≤ 0.79) were found for intra-rater reliability. However, dissimilar inter-rater agreement was detected: Kappa ≤ 0.40 for tibialis anterior and Kappa = 1.00 for vastus lateralis. Conclusion: The SET presented high reliability and moderate agreement in intra-rater evaluations. A fair agreement was found in the inter-rater assessment of the tibialis anterior. Evaluations performed with different electrode sizes did not influence the results. Therefore, the SET should be performed by a unique rater in test retest situations.

An Integrated Multi-Channel Biopotential Recording Analog Front-End IC With Area-Efficient Driven-Right-Leg Circuit.

A multi-channel biopotential recording analog front-end (AFE) with a fully integrated area-efficient driven-right-leg (DRL) circuit is presented in this paper. The proposed AFE includes 10 channels of low-noise capacitive coupled instrumentation amplifier (CCIA), one shared 10-bit SAR ADC and a fully integrated DRL to enhance the system-level common-mode rejection ratio (CMRR). The proposed DRL circuit senses the common-mode at the CCIA output so that the AFE gain is reused as the DRL loop gain. Therefore, area efficient unit-gain buffer with small averaging capacitors can be used in DRL circuit to reduce the circuit area significantly. The proposed AFE has been implemented in a standard 0.18-µm CMOS process. The DRL circuit achieved more than 85% chip area reduction compared to the state-of-art on-chip DRL circuits and maximum 60 dB enhancement to system-level CMRR. Measurement results show high/low AFE gain of 60 dB/54 dB respectively with 1 µA/channel current consumption under 1.0 V power supply. The measured AFE input-referred noise in 1 Hz - 10k Hz range is 4.2 µVrms and the maximum system-level CMRR is 110 dB.

A high-performance 8 nV/√Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals.

BACKGROUND: It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals. METHODS: To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. RESULTS: To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented. CONCLUSIONS: The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5-500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments.

Latency shift in compound muscle action potentials during electroneurography in facial palsy.

OBJECTIVE: Electroneurography (ENoG) reliably predicts the prognosis of facial palsy. However, the results of ENoG are dependent on the location, where the wave is detected, as a compound muscle action potential (CMAP) arising from the facial muscles. To minimize errors in prognostic prediction, we analysed the latencies of facial CMAPs. MATERIALS AND METHODS: Fifty-seven patients with unilateral peripheral facial palsy and 24 healthy volunteers were enrolled. Amplitudes, negative peak latencies (NPL), and rise latencies (RL) of CMAPs were measured on the paralysed and healthy sides in patients and in healthy volunteers. The relationships of these latencies with ENoG values and the lowest House-Brackmann (H-B) scores were also analysed. RESULTS: The amplitude of CMAP on the paralysed side was smaller, and NPL and RL were longer, than those on the healthy side in patients and healthy volunteers (p < 0.01). In patients, there was no difference in NPL between the ENoG < 40% group and the ENoG ≥ 40% group. Conversely, there was a significant difference in RL between the ENoG < 40% group and ENoG ≥ 40% group (p = 0.03). No relationships were observed between NPL or RL and the lowest H-B score. CONCLUSIONS: NPL and RL of CMAP on the paralysed side were equivalent or longer than those on the healthy side. During ENoG for facial palsy, CMAP should be measured on the healthy side first, and then detected (and the amplitude measured) on the paralysed side with reference to CMAP latency on the healthy side, to reduce errors in detecting facial CMAPs.

Instrumentation for electrodiagnostic studies.

The instrument and accessories are an important part of the electrodiagnostic (EDX) testing. Their functional understanding is useful to recognize and reduce various artifacts and noise/interference in the signal. In this review, we will describe the technical specifications of various components of the instrument, and their effect on signals and noise. This will be illustrated using example of electromyography and nerve conduction studies. However the same principles also apply to other modalities of testing. We will also provide general strategies to reduce noise and artifacts, followed by some modality specific examples.

A new methodology to record from human primary afferents provides insight for somatosensory neuroprosthetics.

Muscle spindles are integral to proprioception and their behavior is of particular interest for the design of somatosensory neuroprostheses. Prior knowledge about human muscle spindles has been limited to microneurography recordings in peripheral nerves using joint movements that do not disrupt the electrode. Recent studies demonstrate a new methodology for studying the afferent encoding of proprioception during freestanding, providing important information for neural engineering and the broader scientific community (Knellwolf TP, Burton AR, Hammam E, Macefield VG. J Neurophysiol 120: 953-959, 2018; Knellwolf TP, Burton AR, Hammam E, Macefield VG. J Neurophysiol 121: 74-84, 2019; Macefield VG, Knellwolf TP. J Neurophysiol 120: 452-467, 2018).

The Ussing chamber system for measuring intestinal permeability in health and disease.

BACKGROUND: The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn's disease and potentially could have links with colorectal cancer development. The Ussing chamber system can be utilised as a valuable tool for measuring gut integrity. Here we describe step-by-step methodology required to measure intestinal permeability of both mouse and human colonic tissue samples ex vivo, using the latest equipment and software. This system can be modified to accommodate other tissues. METHODS: An Ussing chamber was constructed and adapted to support both mouse and human tissue to measure intestinal permeability, using paracellular flux and electrical measurements. Two mouse models of intestinal inflammation (dextran sodium sulphate treatment and T regulatory cell depletion using C57BL/6-FoxP3DTR mice) were used to validate the system along with human colonic biopsy samples. RESULTS: Distinct regional differences in permeability were consistently identified within mouse and healthy human colon. In particular, mice showed increased permeability in the mid colonic region. In humans the left colon is more permeable than the right. Furthermore, inflammatory conditions induced chemically or due to autoimmunity reduced intestinal integrity, validating the use of the system. CONCLUSIONS: The Ussing chamber has been used for many years to measure barrier function. However, a clear and informative methods paper describing the setup of modern equipment and step-by-step procedure to measure mouse and human intestinal permeability isn't available. The Ussing chamber system methodology we describe provides such detail to guide investigation of gut integrity.

Abnormal respiratory event detection in sleep: A prescreening system with smart wearables.

Sleeping is an important activity to monitor since it has a crucial role in the overall health and well-being of the people and society. In order to diagnose the problems in sleep, different monitoring systems are developed in the literature. The unobtrusiveness, reduced cost, objectiveness, protection of privacy and user-friendliness are the main design considerations and the proposed system design achieves those objectives by utilizing smart wearables, smart watch and smart phone. The accelerometer and heart rate monitor sensors on smart watch and the sound level sensor on the smart phone are activated. The experiments with this system are performed with 17 subjects in a sleep clinic. The data collected from these subjects is used to generate various combinations by employing varied feature extraction, feature selection and sampling approaches. Five different machine learning algorithms are implemented and the classification results are generated using the various combinations of data, training and scoring strategies. The system performance is measured in two ways, the accuracy rate of distinguishing abnormal respiratory events is 85.95% and the classification success of subjects according to the problems in their respiration is one misclassification among 17 subjects. With all the methodology utilized in this study, the proposed system is a novel prescreening tool which recognizes the severity of problems in respiration during sleep.

Early glioma is associated with abnormal electrical events in cortical cultures.

The prodromal stages of some neurological diseases have a distinct electrical profile which can potentially be leveraged for early diagnosis, predicting disease recurrence, monitoring of disease progression, and better understanding of the disease pathology. Gliomas are tumors that originate from glial cells present in the brain and spinal cord. Healthy glial cells support normal neuronal function and play an important role in modulating the regular electrical activity of neurons. However, gliomas can disrupt the normal electrical dynamics of the brain. Though experimental and clinical studies suggest that glioma and injury to glial cells disrupt electrical dynamics of the brain, whether these disruptions are present during the earliest stages of glioma and glial injury are unclear. The primary aim of this study is to investigate the effect of early in vitro glial pathology (glioma and glial injury in specific) on neuronal electrical activity. In particular, we investigated the effect of glial pathology on neural synchronization: an important phenomenon that underlies several central neurophysiological processes (ScienceDirect, 2018 ). We used two in vitro disease samples: (a) a sample in which cortical cultures were treated with anti-mitotic agents that deplete glial cells and (b) a glioma sample in which healthy cortical cells were cultured with CRL-2303 (an aggressive glioma cell line). Healthy cortical culture samples were used as controls. Cultures were established over a glass dish embedded with microelectrodes that permits simultaneous measurement of extracellular electrical activity from multiple sites of the culture. We observed that healthy cortical cultures produce spontaneous and synchronized oscillations which were attenuated in the absence of glial cells. The presence of glioma was associated with the emergence of two types of "abnormal electrical activity" each with distinct amplitude and frequency profile. Our results indicate that even early stages of glioma and glial injury are associated with distinct changes in neuronal electrical activity. Graphical abstract.

Quantitative separation of the depressive phase of bipolar disorder and major depressive disorder using electrovestibulography.

Objectives: No electrophysiological, neuroimaging or genetic markers have been established that strongly relate to the diagnostic separation of bipolar disorder (BD) and major depressive disorder (MDD). This paper's objective is to describe the potential of features, extracted from the recording of electrical activity from the outer ear canal, in a process called electrovestibulography (EVestG), for identifying depressed and partly remitted/remitted MDD and BD patients from each other.Methods: From EVestG data four sensory vestibulo-acoustic features were extracted from both background (no movement) and using a single supine-vertical translation stimulus to distinguish 27 controls, 39 MDD and 43 BD patients.Results: Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 78-83% (2-3 features), 80-81% (1-2 features) and 66-68% (3 features) accuracies for separation of MDD from BD, controls from depressed (BD & MDD) and the 3-way separation of BD from MDD from control groups, respectively. The main limitations of this study were the inability to fully disentangle the impact of prescribed medication from the responses and also the limited sample size.Conclusions: EVestG features can reliably identify depressed and partly remitted/remitted MDD and BD patients from each other.

Magnetoenterography for the Detection of Partial Mesenteric Ischemia.

BACKGROUND: Acute mesenteric ischemia represents a life-threatening gastrointestinal condition. A noninvasive diagnostic modality that identifies mesenteric ischemia patients early in the disease process will enable early surgical intervention. Previous studies have identified significant changes in the small-bowel electrical slow-wave parameters during intestinal ischemia caused by total occlusion of the superior mesenteric artery. The purpose of this study was to use noninvasive biomagnetic techniques to assess functional physiological changes in intestinal slow waves in response to partial mesenteric ischemia. METHODS: We induced progressive intestinal ischemia in normal porcine subjects (n = 10) by slowly increasing the occlusion of the superior mesenteric artery at the following percentages of baseline flow: 50%, 75%, 90%, and 100% while simultaneous transabdominal magnetoenterogram (MENG) and serosal electromyogram (EMG) recordings were being obtained. RESULTS: A statistically significant serosal EMG amplitude decrease was observed at 100% occlusion compared with baseline, whereas no significant change was observed for MENG amplitude at any progressive occlusion levels. MENG recordings showed significant changes in the frequency and percentage of power distributed in bradyenteric and normoenteric frequency ranges at 50%, 75%, 90%, and 100% vessel occlusions. In serosal EMG recordings, a similar percent power distribution (PPD) effect was observed at 75%, 90%, and 100% occlusion levels. Serosal EMG showed a statistically significant increase in tachyenteric PPD at 90% and 100% occlusion. We observed significant increase in tachyenteric PPD only at the 100% occlusion level in MENG recordings. CONCLUSIONS: Ischemic changes in the intestinal slow wave can be detected early and noninvasively even with partial vascular occlusion. Our results suggest that noninvasive MENG may be useful for clinical diagnosis of partial mesenteric ischemia.

Validity and reliability of a point-of-care nerve conduction device in diabetes patients.

AIMS/INTRODUCTION: Although nerve conduction study (NCS) using a standard electromyography system (EMGS) is considered to be the gold standard in evaluating diabetic polyneuropathy, this examination requires expensive equipment and well-trained technicians. We aimed to validate a point-of-care device, NC-stat/DPNCheck™, that has been developed for widespread use of NCS in diabetic polyneuropathy. MATERIALS AND METHODS: Diabetes patients underwent two kinds of NCS: DPNCheck™ and electromyography system. Inter-/intrarater reliability of DPNCheck™ were also determined by the intraclass correlation coefficient. RESULTS: A total of 57 patients were evaluated. The parameters of NCS between the two methods correlated well (r = 0.7734 for the sural nerve conduction velocity, r = 0.6155 for the amplitude of sural nerve action potential). The intraclass correlation coefficients were excellent (intrarater: the velocity 0.767, the amplitude 0.811; interrater: the velocity 0.974, the amplitude 0.834). CONCLUSIONS: The point-of-care device has excellent reproducibility and good agreement with standard electromyography system. The device might be useful to evaluate diabetic polyneuropathy.

Physiological Sensing Now Open to the World: New Resources Are Allowing Us to Learn, Experiment, and Create Imaginative Solutions for Biomedical Applications.

With the advent of low-cost computing platforms, such as Arduino (http://www.arduino.cc) and Raspberry Pi (http://www.raspberrypi.org), it has become clear that lowering the cost barrier and shortening the learning curve, with the backing of a motivated community, would play a transformational role in the way people learn, experiment, and create imaginative solutions to outstanding problems that can benefit from embedded systems.