What Ultrasound Can and Cannot Do in Implantable Medical Device Communications.

Modern Active Medical Implantable Devices require communications to transmit information to the outside world or other implantable sub-systems. This can include physiological data, diagnostics, and parameters to optimise the therapeutic protocol. The available options are to use optical, radiofrequency, or ultrasonic communications. However, in all cases, transmission becomes more difficult with deeper transmission through tissue. Challenges include absorption and scattering by tissue, and the need to ensure there are no undesirable heating effects. As such, this paper aims to review research progress in using ultrasound as an alternative for deep tissue communications. We provide an empirical review of the technology and communication protocols that different groups have used, as well as comparing the implications in terms of penetration depth, implant size, and data rate. We conclude that this technique has promise for deeper implants and for intrabody communications between implantable devices (intrabody networks).

A Closed-Loop Optogenetic Platform.

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface. We include commercial components to validate performance, with the ultimate aim of translating this approach to humans. In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications. The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics (CANDO) Control System (CS) that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). Here we describe the design and implementation of this system, and demonstrate how it can be used to modulate neuronal oscillations in vitro and in vivo.

Detection of Simulated Tactile Gratings by Electro-Static Friction Show a Dependency on Bar Width for Blind and Sighted Observers, and Preliminary Neural Correlates in Sighted Observers.

The three-dimensional micro-structure of physical surfaces produces frictional forces that provide sensory cues about properties of felt surfaces such as roughness. This tactile information activates somatosensory cortices, and frontal and temporal brain regions. Recent advances in haptic-feedback technologies allow the simulation of surface micro-structures via electro-static friction to produce touch sensations on otherwise flat screens. These sensations may benefit those with visual impairment or blindness. The primary aim of the current study was to test blind and sighted participants' perceptual sensitivity to simulated tactile gratings. A secondary aim was to explore which brain regions were involved in simulated touch to further understand the somatosensory brain network for touch. We used a haptic-feedback touchscreen which simulated tactile gratings using digitally manipulated electro-static friction. In Experiment 1, we compared blind and sighted participants' ability to detect the gratings by touch alone as a function of their spatial frequency (bar width) and intensity. Both blind and sighted participants showed high sensitivity to detect simulated tactile gratings, and their tactile sensitivity functions showed both linear and quadratic dependency on spatial frequency. In Experiment 2, using functional magnetic resonance imaging, we conducted a preliminary investigation to explore whether brain activation to physical vibrations correlated with blindfolded (but sighted) participants' performance with simulated tactile gratings outside the scanner. At the neural level, blindfolded (but sighted) participants' detection performance correlated with brain activation in bi-lateral supplementary motor cortex, left frontal cortex and right occipital cortex. Taken together with previous studies, these results suggest that there are similar perceptual and neural mechanisms for real and simulated touch sensations.

A scalable data transmission scheme for implantable optogenetic visual prostheses.

OBJECTIVE: This work described a video information processing scheme for optogenetic forms of visual cortical prosthetics. APPROACH: The architecture is designed to perform a processing sequence: Initially simplifying the scene, followed by a pragmatic visual encoding scheme which assumes that initially optical stimulation will be stimulating bulk neural tissue rather than driving individual phosphenes. We demonstrate an optical encoder, combined with what we called a zero-run length encoding (zRLE) video compression and decompression scheme-to wirelessly transfer information to an implantable unit in an efficient manner. In the final step, we have incorporated an even power distribution driver to prevent excessive power fluctuations in the optogenetic driving. SIGNIFICANCE: The key novelty in this work centres on the completeness of the scheme, the new zRLE compression algorithm and our even power distributor. MAIN RESULTS: Furthermore, although the paper focusses on the algorithm, we confirm that it can be implemented on real time portable processing hardware which we will use for our visual prosthetics.

A novel hybrid technique to fabricate silicon-based micro-implants with near defect-free quality for neuroprosthetics application.

This paper introduces a new hybrid microfabrication technique which combines ultra-precision micro-milling and a ductile sacrificial material deposition process to fabricate a silicon-based implant for neuroprosthetics applications with near defect-free quality at several hundreds of micrometres in thickness. The sacrificial materials can influence the quality of silicon during machining. The cutting mechanism and feasibility of the hybrid technique are studied by molecular dynamics (MD) simulations and experiments. Due to the complexity of modelling PMMA and SU-8 structures in MD environment, only copper was modelled as the simulation is intended to understand the performance of using a ductile sacrificial layer structure in silicon machining. MD analysis shows that the reduced stress intensity and subsurface damage were mainly attributed to workpiece plasticity enhancement, where its mechanism was contributed by better deformability of the ductile sacrificial layer and enhanced thermal softening from the heat generated by the high interfacial stress between the sacrificial layer and silicon substrate. Despite the MD simulation and experiment having different machining scale in terms of cutting parameters, phenomenal behaviours of the cutting performance when observed under the experimental conditions are in good agreement with simulation. Experimental verification shows that near defect-free quality was achieved at large cutting depth of 150 µm when silicon is coated either with PMMA or SU-8. An exemplary implant structure was also fabricated to better demonstrate the hybrid technique's capability. In addition, the hybrid technique will be beneficial for low volume high customisation applications as it is a serial process.

The Neural Engine: A Reprogrammable Low Power Platform for Closed-Loop Optogenetics.

Brain-machine Interfaces (BMI) hold great potential for treating neurological disorders such as epilepsy. Technological progress is allowing for a shift from open-loop, pacemaker-class, intervention towards fully closed-loop neural control systems. Low power programmable processing systems are therefore required which can operate within the thermal window of 2° C for medical implants and maintain long battery life. In this work, we have developed a low power neural engine with an optimized set of algorithms which can operate under a power cycling domain. We have integrated our system with a custom-designed brain implant chip and demonstrated the operational applicability to the closed-loop modulating neural activities in in-vitro and in-vivo brain tissues: the local field potentials can be modulated at required central frequency ranges. Also, both a freely-moving non-human primate (24-hour) and a rodent (1-hour) in-vivo experiments were performed to show system reliable recording performance. The overall system consumes only 2.93 mA during operation with a biological recording frequency 50 Hz sampling rate (the lifespan is approximately 56 hours). A library of algorithms has been implemented in terms of detection, suppression and optical intervention to allow for exploratory applications in different neurological disorders. Thermal experiments demonstrated that operation creates minimal heating as well as battery performance exceeding 24 hours on a freely moving rodent. Therefore, this technology shows great capabilities for both neuroscience in-vitro/in-vivo applications and medical implantable processing units.

A current-mode system to self-measure temperature on implantable optoelectronics.

BACKGROUND: One of the major concerns in implantable optoelectronics is the heat generated by emitters such as light emitting diodes (LEDs). Such devices typically produce more heat than light, whereas medical regulations state that the surface temperature change of medical implants must stay below + 2 °C. The LED's reverse current can be employed as a temperature-sensitive parameter to measure the temperature change at the implant's surface, and thus, monitor temperature rises. The main challenge in this approach is to bias the LED with a robust voltage since the reverse current is strongly and nonlinearly sensitive to the bias voltage. METHODS: To overcome this challenge, we have developed an area-efficient LED-based temperature sensor using the LED as its own sensor and a CMOS electronic circuit interface to ensure stable bias and current measurement. The circuit utilizes a second-generation current conveyor (CCII) configuration to achieve this and has been implemented in 0.35 µm CMOS technology. RESULTS: The developed circuits have been experimentally characterized, and the temperature-sensing functionality has been tested by interfacing different mini-LEDs in saline models of tissue prior to in vivo operation. The experimental results show the functionality of the CMOS electronics and the efficiency of the CCII-based technique with an operational frequency up to 130 kHz in achieving a resolution of 0.2 °C for the surface temperature up to + 45 °C. CONCLUSIONS: We developed a robust CMOS current-mode sensor interface which has a reliable CCII to accurately convey the LED's reverse current. It is low power and robust against power supply ripple and transistor mismatch which makes it reliable for sensor interface. The achieved results from the circuit characterization and in vivo experiments show the feasibility of the whole sensor interface in monitoring the tissue surface temperature in optogenetics.

Ultrasound Intra Body Multi Node Communication System for Bioelectronic Medicine.

The coming years may see the advent of distributed implantable devices to support bioelectronic medicinal treatments. Communication between implantable components and between deep implants and the outside world can be challenging. Percutaneous wired connectivity is undesirable and both radiofrequency and optical methods are limited by tissue absorption and power safety limits. As such, there is a significant potential niche for ultrasound communications in this domain. In this paper, we present the design and testing of a reliable and efficient ultrasonic communication telemetry scheme using piezoelectric transducers that operate at 320 kHz frequency. A key challenge results from the multi-propagation path effect. Therefore, we present a method, using short pulse sequences with relaxation intervals. To counter an increasing bit, and thus packet, error rate with distance, we have incorporated an error correction encoding scheme. We then demonstrate how the communication scheme can scale to a network of implantable devices. We demonstrate that we can achieve an effective, error-free, data rate of 0.6 kbps, which is sufficient for low data rate bioelectronic medicine applications. Transmission can be achieved at an energy cost of 642 nJ per bit data packet using on/off power cycling in the electronics.

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.

A high-performance 4 nV (√Hz)-1 analog front-end architecture for artefact suppression in local field potential recordings during deep brain stimulation.

OBJECTIVE: Recording of local field potentials (LFPs) during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, existing recording systems lack the ability to provide artefact-free high-frequency (>100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. APPROACH: To solve this problem, we designed and developed a novel, low-noise and versatile analog front-end (AFE) that uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, we assessed the performance of the realised AFE by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). A full performance comparison between the proposed AFE and an identical AFE, equipped with an 8th order analog Bessel notch filter, was also conducted. MAIN RESULTS: A high-performance, 4 nV ([Formula: see text])-1 AFE that is capable of recording nV-scale signals was designed in accordance with the imposed specifications. Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5-250 Hz) during stimulation. Its sensing and stimulation artefact suppression capabilities outperformed the capabilities of the AFE equipped with the Bessel notch filter. SIGNIFICANCE: The designed AFE can precisely record LFP signals, in and without the presence of either unipolar or bipolar DBS, which renders it as a functional and practical AFE architecture to be utilised in a wide range of applications and environments. This work paves the way for the development of externalized research tools for closed-loop neuromodulation that use low- and higher-frequency LFPs as control signals.

Design Considerations for Artefact-Free Optoelectronic Systems.

This paper proposes design considerations that need to be followed in order to eliminate potential sources of artefact that could distort a recorded neural signal. The artefact that appears in a recorded signal has a combination of potential sources each of which contributes towards its formation. As such, these sources of artefact have been addressed in three main categories: a) electronics artefact, b) encapsulation artefact and c) interface artefact. Each source (component) is analyzed further and appropriate design techniques and considerations are suggested towards its mitigation.

Wireless Ultrasonic Communication for Biomedical Injectable Implantable Device.

This paper presents a design and implementation of an ultrasonic wireless communication link for an injectable biomedical implanted device. The results address how the ultrasound link encounter from the multiple paths propagation effect. The ultrasound link characterized in term of channel impulse response and power transmission losses against the depth of the implant, the achieved data transmission rate was 70 Kbps and the signal to noise ratio was (30, 35 and 47) dB at a transmission voltage of (1.8, 3.3 and 20) V peak to peak in 12 cm depth. The transmission loss increases as the depth of the implant increases. The ultrasound link represented by two piezoelectric transducers that operate in 320 KHz radial resonance frequency.

Comparison between Different Optical Systems for Optogenetics based Head Mounted Device for Retina Pigmentosa.

Optogenetics is a fast growing neuromodulation techniques as it can remotely stimulate neural activities of a genetically modified cells. The advantage of remotely controlling the neural activity triggered researchers to implement a headset to externally stimulate retina cells for people with retina pigmentosa. The wearable device requires an efficient optical system to focus the transmitted light pattern into the retina surface. In this work, three different lenses; contact lens, folded prism and linear lenses are used to evaluate the headset performance. A 90x90 µLED display is used as a light source and the optical efficiency for each lens is measured for different points over the lens area. Moreover, the impact of each lens on the headset performance in power and processing will be discussed in this work.

Modelling Optogenetic Subthreshold Effects.

We develop a system-level approach to modelling optogenetic-neurons firing behaviour in in-vivo conditions. This approach contains three sub-modules: 1) a Mie/Rayleigh scattering mode of light penetration in tissue; 2) a classic likelihood Poisson spiking train model; 3) a 4-state model of the Channelrhodopsin-2 (ChR2) channel added to a CA3 neuron Hodgkin-Huxley model. We first investigate opto-neurons lightto-spike mechanisms in an in-vivo model: the background noise (synaptic currents) play a dominant role in generating spikes rather than light intensities as for in-vitro conditions (Typically the required light intensity is less than 0.3 mW/mm2 for in-vivo). Then the spiking fidelity is analyzed for different background noise levels. Next, by combining light penetration profiles, we show how neuron firing rates decay as tissue distance increases, for a 2D dimensional cross-section. This preliminary data clearly demonstrate that at given light stimulation protocol, the maximum effected distance in-vivo is 250 µm with small frequency decay rates, while for in-vitro is 50µm with considerable frequency decay rates. Therefore, the developed model can be used for designing sensible light stimulation strategies in-vivo and opto-electronics systems.

A Scalable Optoelectronic Neural Probe Architecture With Self-Diagnostic Capability.

There is a growing demand for the development of new types of implantable optoelectronics to support both basic neuroscience and optogenetic treatments for neurological disorders. Target specification requirements include multi-site optical stimulation, programmable radiance profile, safe operation, and miniaturization. It is also preferable to have a simple serial interface rather than large numbers of control lines. This paper demonstrates an optrode structure comprising of a standard complementary metal-oxide-semiconductor process with 18 optical stimulation drivers. Furthermore, diagnostic sensing circuitry is incorporated to determine the long-term functionality of the photonic elements. A digital control system is incorporated to allow independent multisite control and serial communication with external control units.

A head mounted device stimulator for optogenetic retinal prosthesis.

OBJECTIVE: Our main objective is to demonstrate that compact high radiance gallium nitride displays can be used with conventional virtual reality optics to stimulate an optogenetic retina. Hence, we aim to introduce a non-invasive approach to restore vision for people with conditions such as retinitis pigmentosa where there is a remaining viable communication link between the retina and the visual cortex. APPROACH: We design and implement the headset using a high-density µLED matrix, Raspberry Pi, microcontroller from NXP and virtual reality lens. Then, a test platform is developed to evaluate the performance of the headset and the optical system. Furthermore, image simplification algorithms are used to simplify the scene to be sent to the retina. Moreover, in vivo evaluation of the genetically modified retina response at different light intensity is discussed to prove the reliability of the proposed system. MAIN RESULTS: We demonstrate that in keeping with regulatory guidance, the headset displays need to limit their luminance to 90 kcd m-2. We demonstrate an optical system with 5.75% efficiency which allows for 0.16 mW mm-2 irradiance on the retina within the regulatory guidance, but which is capable of an average peak irradiance of 1.35 mW mm-2. As this is lower than the commonly accepted threshold for channelrhodopsin-2, we demonstrate efficacy through an optical model of an eye onto a biological retina. SIGNIFICANCE: We demonstrate a fully functional 8100-pixel headset system including software/hardware which can operate on a standard consumer battery for periods exceeding a 24 h recharge cycle. The headset is capable of delivering enough light to stimulate the genetically modified retina cells and also keeping the amount of light below the regulation threshold for safety.

On-Probe Neural Interface ASIC for Combined Electrical Recording and Optogenetic Stimulation.

Neuromodulation technologies are progressing from pacemaking and sensory operations to full closed-loop control. In particular, optogenetics-the genetic modification of light sensitivity into neural tissue allows for simultaneous optical stimulation and electronic recording. This paper presents a neural interface application-specified integrated circuit (ASIC) for intelligent optoelectronic probes. The architecture is designed to enable simultaneous optical neural stimulation and electronic recording. It provides four low noise (2.08  µV) recording channels optimized for recording local field potentials (LFPs) (0.1-300 Hz bandwidth, 5 mV range, sampled 10-bit@4 kHz), which are more stable for chronic applications. For stimulation, it provides six independently addressable optical driver circuits, which can provide both intensity (8-bit resolution across a 1.1 mA range) and pulse-width modulation for high-radiance light emitting diodes (LEDs). The system includes a fully digital interface using a serial peripheral interface (SPI) protocol to allow for use with embedded controllers. The SPI interface is embedded within a finite state machine (FSM), which implements a command interpreter that can send out LFP data whilst receiving instructions to control LED emission. The circuit has been implemented in a commercially available 0.35  µm CMOS technology occupying a 1.95 mm 1.10 mm footprint for mounting onto the head of a silicon probe. Measured results are given for a variety of bench-top, in vitro and in vivo experiments, quantifying system performance and also demonstrating concurrent recording and stimulation within relevant experimental models.

Extraspectral Imaging for Improving the Perceived Information Presented in Retinal Prosthesis.

Retinal prosthesis is steadily improving as a clinical treatment for blindness caused by retinitis pigmentosa. However, despite the continued exciting progress, the level of visual return is still very poor. It is also unlikely that those utilising these devices will stop being legally blind in the near future. Therefore, it is important to develop methods to maximise the transfer of useful information extracted from the visual scene. Such an approach can be achieved by digitally suppressing less important visual features and textures within the scene. The result can be interpreted as a cartoon-like image of the scene. Furthermore, utilising extravisual wavelengths such as infrared can be useful in the decision process to determine the optimal information to present. In this paper, we, therefore, present a processing methodology that utilises information extracted from the infrared spectrum to assist in the preprocessing of the visual image prior to conversion to retinal information. We demonstrate how this allows for enhanced recognition and how it could be implemented for optogenetic forms of retinal prosthesis. The new approach has been quantitatively evaluated on volunteers showing 112% enhancement in recognizing objects over normal approaches.

Opto-electro-thermal optimization of photonic probes for optogenetic neural stimulation.

Implantable photonic probes are of increasing interest to the field of biophotonics and in particular, optogenetic neural stimulation. Active probes with onboard light emissive elements allow for electronic multiplexing and can be manufactured through existing microelectronics methods. However, as the optogenetics field moves towards clinical practice, an important question arises as to whether such probes will cause excessive thermal heating of the surrounding tissue. Light emitting diodes typically produce more heat than light. The resultant temperature rise of the probe surface therefore needs to be maintained under the regulatory limit of 2°C. This work combines optical and thermal modelling, which have been experimental verified. Analysis has been performed on the effect of probe/emitter geometries, emitter, and radiance requirements. Finally, the effective illumination volume has been calculated within thermal limits for different probe emitter types and required thresholds.

Self-sensing of temperature rises on light emitting diode based optrodes.

OBJECTIVE: This work presents a method to determine the surface temperature of microphotonic medical implants like LEDs. Our inventive step is to use the photonic emitter (LED) employed in an implantable device as its own sensor and develop readout circuitry to accurately determine the surface temperature of the device. APPROACH: There are two primary classes of applications where microphotonics could be used in implantable devices; opto-electrophysiology and fluorescence sensing. In such scenarios, intense light needs to be delivered to the target. As blue wavelengths are scattered strongly in tissue, such delivery needs to be either via optic fibres, two-photon approaches or through local emitters. In the latter case, as light emitters generate heat, there is a potential for probe surfaces to exceed the 2 °C regulatory. However, currently, there are no convenient mechanisms to monitor this in situ. MAIN RESULTS: We present the electronic control circuit and calibration method to monitor the surface temperature change of implantable optrode. The efficacy is demonstrated in air, saline, and brain. SIGNIFICANCE: This paper, therefore, presents a method to utilize the light emitting diode as its own temperature sensor.