A Resonant Coupler for Subcutaneous Implant.

A resonator coupler for subcutaneous implants has been developed with a new impedance matching pattern added to the conventional loop antenna. The tuning element of a concentric metal pad contributes distributed capacitance and inductance to the planar inductive loop and improves resonance significantly. It provides a better qualify factor for resonant coupling and a much lower reflection coefficient for the implant electronics. Practical constraints are taken into account for designs including the requirement of operation within a regulated frequency band and the limited thickness for a monolithic implant. In this work, two designs targeting to operate in the two industrial, scientific, and medical (ISM) bands at 903 MHz and 2.45 GHz are considered. The tuning metal pad improves their resonances significantly, compared to the conventional loop designs. Since it is difficult to tune the implant antenna after implantation, the effects of tissue depth variations due to the individual's surgery and the appropriate implant depths are investigated. Simulations conducted with the dielectric properties of human skin documented in the literature are compared to measurements done with hydrated ground pork as phantoms. Experiments and simulations are conducted to explain the discrepancies in frequency shifts due to the uses of pork phantoms. The design method is thus validated for uses on human skin. A noninvasive localization method to identify the implant under the skin has been examined and demonstrated by both simulations and measurements. It can efficiently locate the subcutaneous implant based on the high quality-factor resonance owing to the tuning elements in both implant and transmitter couplers. The planar resonant coupler for wireless power transfer shows good performance and promise in subcutaneous applications for implants.

Deep learning-based framework for cardiac function assessment in embryonic zebrafish from heart beating videos.

Zebrafish is a powerful and widely-used model system for a host of biological investigations, including cardiovascular studies and genetic screening. Zebrafish are readily assessable during developmental stages; however, the current methods for quantifying and monitoring cardiac functions mainly involve tedious manual work and inconsistent estimations. In this paper, we developed and validated a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) based on a U-net deep learning model for automated assessment of cardiovascular indices, such as ejection fraction (EF) and fractional shortening (FS) from microscopic videos of wildtype and cardiomyopathy mutant zebrafish embryos. Our approach yielded favorable performance with accuracy above 90% compared with manual processing. We used only black and white regular microscopic recordings with frame rates of 5-20 frames per second (fps); thus, the framework could be widely applicable with any laboratory resources and infrastructure. Most importantly, the automatic feature holds promise to enable efficient, consistent, and reliable processing and analysis capacity for large amounts of videos, which can be generated by diverse collaborating teams.

Electromagnetic interference in intraoperative monitoring of motor evoked potentials and a wireless solution.

Intraoperative neurophysiological monitoring (IONM) is utilized to minimize neurological morbidity during spine surgery. Transcranial motor evoked potentials (TcMEPs) are principal IONM signals in which the motor cortex of the subject is stimulated with electrical pulses and the evoked potentials are recorded from the muscles of interest. Currently available monitoring systems require the connection of 40-60 lengthy lead wires to the patient. These wires contribute to a crowded and cluttered surgical environment, and limit the maneuverability of the surgical team. In this work, it was demonstrated that the cumbersome wired system is vulnerable to electromagnetic interference (EMI) produced by operating room (OR) equipment. It was hypothesized that eliminating the lengthy recording wires can remove the EMI induced in the IONM signals. Hence, a wireless system to acquire TcMEPs was developed and validated through bench-top and animal experiments. Side-by-side TcMEPs acquisition from the wired and wireless systems in animal experiments under controlled conditions (absence of EMI from OR equipment) showed comparable magnitudes and waveforms, thus demonstrating the fidelity in the signal acquisition of the wireless solution. The robustness of the wireless system to minimize EMI was compared with a wired-system under identical conditions. Unlike the wired-system, the wireless system was not influenced by the electromagnetic waves from the C-Arm X-ray machine and temperature management system in the OR.

Wireless Power Transfer for Autonomous Wearable Neurotransmitter Sensors.

In this paper, we report a power management system for autonomous and real-time monitoring of the neurotransmitter L-glutamate (L-Glu). A low-power, low-noise, and high-gain recording module was designed to acquire signal from an implantable flexible L-Glu sensor fabricated by micro-electro-mechanical system (MEMS)-based processes. The wearable recording module was wirelessly powered through inductive coupling transmitter antennas. Lateral and angular misalignments of the receiver antennas were resolved by using a multi-transmitter antenna configuration. The effective coverage, over which the recording module functioned properly, was improved with the use of in-phase transmitter antennas. Experimental results showed that the recording system was capable of operating continuously at distances of 4 cm, 7 cm and 10 cm. The wireless power management system reduced the weight of the recording module, eliminated human intervention and enabled animal experimentation for extended durations.

Batteryless implantable dual-sensor capsule for esophageal reflux monitoring.

BACKGROUND: Chronic GERD affects approximately 15% of adults in the United States and is one of the most prevalent clinical conditions involving the GI tract. The commercial tools for monitoring GERD include multichannel intraluminal impedance (MII) probes and pH-sensing capsules. However, MII probes cause discomfort, which alters patients' regular activities, whereas the pH-sensing capsule lacks the ability to detect weak or nonacid episodes, misses reflux episodes with similar pH values, and has a limited sampling rate and battery life. OBJECTIVE: To develop and test an implantable batteryless dual-sensor capsule that can be used to diagnose and monitor GERD. DESIGN: The implanted capsule is wirelessly powered by an external device. Simulated reflux episodes were created in 3 live porcine models. Impedance and pH data were continuously measured and recorded. INTERVENTION: The implant capsule was placed in the esophagus along with a commercial pH-sensing capsule for comparison. MAIN OUTCOME MEASUREMENTS: Precise impedance and pH readouts were obtained and compared with those from a commercial pH-sensing capsule. RESULTS: The wireless energy supplied by the external unit was strong enough to power the implant. The pH sensor accurately measured pH levels and the impedance sensor precisely located the reflux episodes. LIMITATION: Simulated reflux events in a pig model. CONCLUSION: Our wireless sensors are reliable in operation and provide accurate assessment of simulated reflux episodes. The entire device can potentially be used to diagnose and monitor GERD.

An integrated µLED optrode for optogenetic stimulation and electrical recording.

In this letter, we developed an integrated neural probe prototype for optogenetic stimulation by microscale light-emitting diode (µLED) and simultaneous recording of neural activities with microelectrodes on a single-polyimide platform. Optogenetics stimulates in vivo neural circuits with high-cellular specificity achieved by genetic targeting and precise temporal resolution by interaction of light-gated ion channels with optical beam. In our newly developed optrode probe, during optogenetic stimulation of neurons, continuous sensing of neuronal activities in vicinity of the activation site can provide feedback to stimulation or examine local responses in signal pathways. In the device, focusing the light from the µLED was achieved with an integrated photo-polymerized lens. The efficacy of the optrode for cortical stimulation and recording was tested on mice visual cortex neurons expressing channelrhodopsin-2. Stimulation intensity and frequency-dependent spiking activities of visual cortex were recorded. Our device has shown advantages over fiber-coupled laser-based optrode in terms of closed-loop integration, single-implant compactness and lower electrical power requirements, which would be clinically applicable for future prosthetic applications in personalized medicine.

A digital wireless system for closed-loop inhibition of nociceptive signals.

Neurostimulation of the spinal cord or brain has been used to inhibit nociceptive signals in pain management applications. Nevertheless, most of the current neurostimulation models are based on open-loop system designs. There is a lack of closed-loop systems for neurostimulation in research with small freely-moving animals and in future clinical applications. Based on our previously developed analog wireless system for closed-loop neurostimulation, a digital wireless system with real-time feedback between recorder and stimulator modules has been developed to achieve multi-channel communication. The wireless system includes a wearable recording module, a wearable stimulation module and a transceiver connected to a computer for real-time and off-line data processing, display and storage. To validate our system, wide dynamic range neurons in the spinal cord dorsal horn have been recorded from anesthetized rats in response to graded mechanical stimuli (brush, pressure and pinch) applied in the hind paw. The identified nociceptive signals were used to automatically trigger electrical stimulation at the periaqueductal gray in real time to inhibit their own activities by the closed-loop design. Our digital wireless closed-loop system has provided a simplified and efficient method for further study of pain processing in freely-moving animals and potential clinical application in patients.

An implantable, batteryless, and wireless capsule with integrated impedance and pH sensors for gastroesophageal reflux monitoring.

In this study, a device for gastroesophageal reflux disease (GERD) monitoring has been prototyped. The system consists of an implantable, batteryless and wireless transponder with integrated impedance and pH sensors; and a wearable, external reader that wirelessly powers up the transponder and interprets the transponded radio-frequency signals. The transponder implant with the total size of 0.4 cm × 0.8 cm × 3.8 cm harvests radio frequency energy to operate dual-sensor and load-modulation circuitry. The external reader can store the data in a memory card and/or send it to a base station wirelessly, which is optional in the case of multiple-patient monitoring in a hospital or conducting large-scale freely behaving animal experiments. Tests were carried out to verify the signal transduction reliability in different situations for antenna locations and orientation. In vitro, experiments were conducted in a mannequin model by positioning the sensor capsule inside the wall of a tube mimicking the esophagus. Different liquids with known pH values were flushed through the tube creating reflux episodes and wireless signals were recorded. Live pigs under anesthesia were used for the animal models with the transponder implant attached on the esophageal wall. The reflux episodes were created while the sensor data were recorded wirelessly. The data were compared with those recorded independently by a clinically used wireless pH sensor capsule placed next to our implant transponder. The results showed that our transponder detected every episode in both acid and nonacid nature, while the commercial pH sensor missed events that had similar, repeated pH values, and failed to detect pH values higher than 10. Our batteryless transponder does not require a battery thus allowing longer diagnosis and prognosis periods to monitor drug efficacy, as well as providing accurate assessment of GERD symptoms.

Development of innovative techniques for the endoscopic implantation and securing of a novel, wireless, miniature gastrostimulator (with videos).

BACKGROUND: Gastric stimulation via high-frequency, low-energy pulses can provide an effective treatment for gastric dysmotility; however, the current commercially available device requires surgical implantation for long-term stimulation and is powered by a nonrechargeable battery. OBJECTIVE: To test and describe endoscopic implantation techniques and testing of stimulation of a novel, wireless, batteryless, gastric electrical stimulation (GES) device. DESIGN: Endoscopic gastric implantation techniques were implemented, and in vivo gastric signals were recorded and measured in a non-survival swine model (n = 2; 50-kg animals). INTERVENTION: Five novel endoscopic gastric implantation techniques and stimulation of a novel, wireless, batteryless, GES device were tested on a non-survival swine model. MAIN OUTCOME MEASUREMENTS: Feasibility of 5 new endoscopic gastric implantation techniques of the novel, miniature, batteryless, wireless GES device while recording and measurement of in vivo gastric signals. RESULTS: All 5 of the novel endoscopic techniques permitted insertion and securing of the miniaturized gastrostimulator. By the help of these methods and miniaturization of the gastrostimulator, successful GES could be provided without any surgery. The metallic clip attachment was restricted to the mucosal surface, whereas the prototype tacks, prototype spring coils, percutaneous endoscopic gastrostomy wires/T-tag fasteners, and submucosal pocket endoscopic implantation methods attach the stimulator near transmurally or transmurally to the stomach. They allow more secure device attachment with optimal stimulation depth. LIMITATIONS: Non-survival pig studies. CONCLUSION: These 5 techniques have the potential to augment the utility of GES as a treatment alternative, to provide an important prototype for other dysmotility treatment paradigms, and to yield insights for new technological interfaces between non-invasiveness and surgery.

A closed loop feedback system for automatic detection and inhibition of mechano-nociceptive neural activity.

Clinical studies have shown that spinal or cerebral neurostimulation can significantly relieve pain. Current neurostimulators work in an open loop; hence, their efficacy depends on the patient's or physician's comprehension of pain. We have proposed and developed a real-time automatic recognition program with signal processing functions to detect action potentials. By using a wireless neurorecording module, spinal neuronal responses to mechanical stimuli (brush, pressure, and pinch) applied to rats' hind paws were recorded. Nociceptive spinal responses were detected and suppressed by our automated module through delivering electrical stimulation to the periaqueductal gray (PAG). The interspike intervals (ISIs) of the fired action potentials were used to distinguish among the three different mechanical stimuli. Our system was able to detect the neuronal activity intensities and deliver trigger signals to the neurostimulator according to a pre-set threshold in a closed-loop feedback configuration, thereby suppressing excessive activity in spinal cord dorsal horn neurons.

A miniature bidirectional telemetry system for in vivo gastric slow wave recordings.

Stomach contractions are initiated and coordinated by an underlying electrical activity (slow waves), and electrical dysrhythmias accompany motility diseases. Electrical recordings taken directly from the stomach provide the most valuable data, but face technical constraints. Serosal or mucosal electrodes have cables that traverse the abdominal wall, or a natural orifice, causing discomfort and possible infection, and restricting mobility. These problems motivated the development of a wireless system. The bidirectional telemetric system constitutes a front-end transponder, a back-end receiver and a graphical userinter face. The front-end module conditions the analogue signals, then digitizes and loads the data into a radio for transmission. Data receipt at the backend is acknowledged via a transceiver function. The system was validated in a bench-top study, then validated in vivo using serosal electrodes connected simultaneously to a commercial wired system. The front-end module was 35 × 35 × 27 mm3 and weighed 20 g. Bench-top tests demonstrated reliable communication within a distance range of 30 m, power consumption of 13.5 mW, and 124 h operation when utilizing a 560 mAh, 3 V battery. In vivo,slow wave frequencies were recorded identically with the wireless and wired reference systems (2.4 cycles min−1), automated activation time detection was modestly better for the wireless system (5% versus 14% FP rate), and signal amplitudes were modestly higher via the wireless system (462 versus 3 86µV; p<0.001). This telemetric system for slow wave acquisition is reliable,power efficient, readily portable and potentially implantable. The device will enable chronic monitoring and evaluation of slow wave patterns in animals and patients.0967-3334/

Detection of thermal pain in rodents through wireless electrocorticography.

In an effort to detect pain in an objective way, Electrocorticography (ECoG) signals were acquired from male Sprague-Dawley rats in response to thermally induced pain. A wearable, wireless multichannel system was utilized to acquire signals from freely-behaving animals during the experiments. ECoG signals were recorded before (baseline) and during the heat exposure for which animals withdrew their paws in response to the painful feeling. Analysis of the signals revealed a clear, high-amplitude peak at the moment of the paw withdrawal across all four recording channels in each test. Analysis in the frequency domain found the peaks coincided with an abrupt increase of delta rhythms (under 4 Hz). In the baseline, heating, and post-withdrawal segments, these rhythms were relatively low, indicating that the sharp increase in delta activity might be associated with pain. Theta, alpha, beta, and gamma rhythms were also measured, but no significant differences were found between each phase of the signals. These preliminary results are promising; however, more animal models will need to be tested to provide statistically significant results with high confidence.

A wireless system for monitoring transcranial motor evoked potentials.

Intraoperative neurophysiological monitoring (IONM) is commonly used as an attempt to minimize neurological morbidity from operative manipulations. The goal of IONM is to identify changes in the central and peripheral nervous system function prior to irreversible damage. Intraoperative monitoring also has been effective in localizing anatomical structures, including peripheral nerves and sensorimotor cortex, which helps guide the surgeon during dissection. As part of IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) are routinely monitored. However, current wired systems are cumbersome as the wires contribute to the crowded conditions in the operating room and in doing so not only it limits the maneuverability of the surgeon and assistants, but also places certain demand in the total anesthesia required during surgery, due to setup preoperative time needed for proper electrode placement, due to the number and length of the wires, and critical identification of the lead wires needed for stimulation and recording. To address these limitations, we have developed a wireless TcMEP IONM system as a first step toward a multimodality IONM system. Bench-top and animal experiments in rodents demonstrated that the wireless method reproduced with high fidelity, and even increased the frequency bandwidth of the TcMEP signals, compared to wired systems. This wireless system will reduce the preoperative time required for IONM setup, add convenience for surgical staff, and reduce wire-related risks for patients during the operation.

Recognition and inhibition of dorsal horn nociceptive signals within a closed-loop system.

We implemented an integrated system that can acquire neuronal signals from spinal cord dorsal horn neurons, wirelessly transmit the signals to a computer, and recognize the nociceptive signals from three different mechanical stimuli (brush, pressure and pinch). Positive peak detection method was chosen to distinguish between signal spikes. The inter spike intervals (ISIs) were calculated from the identified action potentials (APs) and fed into a numerical array called cluster. When the sum of the ISIs in the cluster reached a critical level, the program recognized the recorded signals as nociceptive inputs. The user has the flexibility to tune both the cluster size and critical threshold for individual's need to reach optimization in pain signal recognition. The program was integrated with a wireless neurostimulator to form a feedback loop to recognize and inhibit nociceptive signals.

A combined wireless neural stimulating and recording system for study of pain processing.

Clinical studies have shown that spinal or cortical neurostimulation could significantly improve pain relief. The currently available stimulators, however, are used only to generate specific electrical signals without the knowledge of physiologically responses caused from the stimulation. We thus propose a new system that can adaptively generate the optimized stimulating signals base on the correlated neuron activities. This new method could significantly improve the efficiency of neurostimulation for pain relief. We have developed an integrated wireless recording and stimulating system to transmit the neuronal signals and to activate the stimulator over the wireless link. A wearable prototype has been developed consisting of amplifiers, wireless modules and a microcontroller remotely controlled by a Labview program in a computer to generate desired stimulating pulses. The components were assembled on a board with a size of 2.5 cm x 5 cm to be carried by a rat. To validate our system, lumbar spinal cord dorsal horn neuron activities of anesthetized rats have been recorded in responses to various types of peripheral graded mechanical stimuli. The stimulation at the periaqueductal gray and anterior cingulate cortex with different combinations of electrical parameters showed a comparable inhibition of spinal cord dorsal horns activities in response to the mechanical stimuli. The Labview program was also used to monitor the neuronal activities and automatically activate the stimulator with designated pulses. Our wireless system has provided an opportunity for further study of pain processing with closed-loop stimulation paradigm in a potential new pain relief method.

Metrology and Standards Needs for Some Categories of Medical Devices.

With rapid advances in meso-, micro- and nano-scale technology devices and electronics, a new generation of advanced medical devices is emerging, which promises medical treatment that is less invasive and more accurate, automated, and effective. We examined the technological and economic status of five categories of medical devices. A set of metrology needs is identified for each of these categories and suggestions are made to address them.