A Linear-Power-Regulated Wireless Power Transfer Method for Decreasing the Heat Dissipation of Fully Implantable Microsystems.

Magnetic coupling resonance wireless power transfer can efficiently provide energy to intracranial implants under safety constraints, and is the main way to power fully implantable brain-computer interface systems. However, the existing maximum efficiency tracking wireless power transfer system is aimed at optimizing the overall system efficiency, but the efficiency of the secondary side is not optimized. Moreover, the parameters of the transmitter and the receiver change nonlinearly in the power control process, and the efficiency tracking mainly depends on wireless communication. The heat dissipation caused by the unoptimized receiver efficiency and the wireless communication delay in power control will inevitably affect neural activity and even cause damage, thus affecting the results of neuroscience research. Here, a linear-power-regulated wireless power transfer method is proposed to realize the linear change of the received power regulation and optimize the receiver efficiency, and a miniaturized linear-power-regulated wireless power transfer system is developed. With the received power control, the efficiency of the receiver is increased to more than 80%, which can significantly reduce the heating of fully implantable microsystems. The linear change of the received power regulation makes the reflected impedance in the transmitter change linearly, which will help to reduce the dependence on wireless communication and improve biological safety in received power control applications.

Binaural hearing restoration with a bilateral fully implantable middle ear implant.

AIM: The fully implantable middle ear implant (C-FI-MEI) is designed for patients with moderate-to-severe sensorineural hearing loss or those with mixed hearing loss. To analyze the audiological post-operative results of subjects bilaterally implanted with C-FI-MEI. MATERIALS AND METHODS: Retrospective study: 14 patients with bilateral, moderate-to-severe, sensorineural or mixed hearing loss were treated. This clinical sample included 14 cases bilaterally implanted (13 sequentially, 1 simultaneously). The evaluation at each follow-up after surgery included otologic examination, a structured interview, and different audiological tests composed of pure tone audiometry, speech in quiet and in noise test, and localization task. The mean follow-up was 67.2 ± 33 months. RESULTS: There were no significant differences between pre and post-operative pure tone averages. The patients showed no significant differences between pre-operatively aided and C-FI-MEI implant-aided conditions in terms of word recognition score. Speech perception in noise under different loudspeaker arrangements and localization tests demonstrated a binaural advantage in bilaterally implanted patients. The mean daily use time was 17.4 and 16.7 h, respectively, for right and left side. CONCLUSION: The results for the 14 patients, bilaterally implanted with C-FI-MEI, suggest that bilateral implantation of fully implantable middle ear hearing devices is an effective procedure. LEVEL OF EVIDENCE: 4.

Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless Pharmacology and Optogenetics.

Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported. The device integrates microscale inorganic light-emitting diodes and microfluidic drug delivery systems with a tiny stretchable multichannel radiofrequency antenna, which not only eliminates the need for bulky batteries but also offers fully wireless, independent control of light and fluid delivery. This design enables a miniature (125 mm3 ), lightweight (220 mg), soft, and flexible platform, thus facilitating seamless implantation and operation in the body without causing disturbance of naturalistic behavior. The proof-of-principle experiments and analytical studies validate the feasibility and reliability of the fully implantable optofluidic systems for use in freely moving animals, demonstrating its potential for wireless in vivo pharmacology and optogenetics.

[Callus distraction and bone transport in the treatment of bone defects]. / Kallusdistraktion und Segmenttransport zur Behandlung von Knochendefekten.

BACKGROUND: The method of "callus distraction" is the only technique which spontaneously produces vascularized bone within the surrounding soft tissues during lengthening reconstructive procedures. Remodeling of the regenerate bone to specific mechanical load can be influenced by the surgeon. In principle, there is no limit to the amount of new bone formation which can be created; this vascularized bone is both resistant to infection and can be created to replace resected infected bone. This is an important prerequisite for the successful treatment of large bone defects. TECHNIQUE: The ring fixator is still a standard tool if no radiological control is available in the operating theater, or in other less sophisticated environments. Over the last 30 years, however, the development of motorized, external and fully implantable systems has made it possible to achieve a significant increase in device implementation, which goes far beyond the standard. RESULTS: High-performance, reliable, custom-made external and fully implantable systems are cost intensive and require special surgical skills, which can only be ensured at specialized centers. However, the complication-free treatment results justify the effort both for the patient and, ultimately, for the cost bearers.

A New Trans-Tympanic Microphone Approach for Fully Implantable Hearing Devices.

Fully implantable hearing devices (FIHDs) have been developed as a new technology to overcome the disadvantages of conventional acoustic hearing aids. The implantable microphones currently used in FIHDs, however, have difficulty achieving high sensitivity to environmental sounds, low sensitivity to body noise, and ease of implantation. In general, implantable microphones may be placed under the skin in the temporal bone region of the skull. In this situation, body noise picked up during mastication and touching can be significant, and the layer of skin and hair can both attenuate and distort sounds. The new approach presently proposed is a microphone implanted at the tympanic membrane. This method increases the microphone's sensitivity by utilizing the pinna's directionally dependent sound collection capabilities and the natural resonances of the ear canal. The sensitivity and insertion loss of this microphone were measured in human cadaveric specimens in the 0.1 to 16 kHz frequency range. In addition, the maximum stable gain due to feedback between the trans-tympanic microphone and a round-window-drive transducer, was measured. The results confirmed in situ high-performance capabilities of the proposed trans-tympanic microphone.

Piezoelectric Multi-Channel Bilayer Transducer for Sensing and Filtering Ossicular Vibration.

This paper presents an acoustic transducer for fully implantable cochlear implants (FICIs), which can be implanted on the hearing chain to detect and filter the ambient sound in eight frequency bands between 250 and 6000 Hz. The transducer dimensions are conventional surgery compatible. The structure is formed with 3  × 3 × 0.36 mm active space for each layer and 5.2 mg total active mass excluding packaging. Characterization of the transducer is carried on an artificial membrane whose vibration characteristic is similar to the umbo vibration. On the artificial membrane, piezoelectric transducer generates up to 320.3 mVpp under 100 dB sound pressure level (SPL) excitation and covers the audible acoustic frequency. The measured signal-to-noise-ratio (SNR) of the channels is up to 84.2 dB. Sound quality of the transducer for fully implantable cochlear implant application is graded with an objective qualification method (PESQ) for the first time in the literature to the best of the knowledge, and scored 3.42/4.5.

Initial Experiences with the Envoy Acclaim® Fully Implanted Cochlear Implant.

Introduction: Cochlear implantation has become the standard of care for the treatment of moderate-to-profound bilateral sensorineural hearing loss. However, current technologies, all of which rely on an external sound processor, have intrinsic limitations that prevent certain activities and diagnostics, thus hampering full integration into a patient's lifestyle. The Envoy Medical (White Bear Lake, MN, USA) Acclaim® fully implanted cochlear implant is a new device currently undergoing testing that has been designed to alleviate many of the current constraints by housing all components within the patient, thus allowing for near-constant use in many environments that are not conducive to a traditional cochlear implant. Methods: As part of an Early Feasibility Study, three adult implant candidates were implanted with the Acclaim® cochlear implant. Surgical video and photography were taken, and initial observations were recorded. Implantation with the Acclaim® device is largely similar to a traditional cochlear implant, with modifications to allow room for the implanted sensor as well as the implantation of a battery in the subcutaneous tissues of the chest. Results: This study demonstrates a step-by-step overview of implanting the Acclaim® and discusses initial insight and experiences with the first three implantations with this new device. Conclusions: All three surgeries proceeded without complication, and at activation, all three patients were hearing through their devices. Surgery is more technically challenging compared to a standard cochlear implant, but the skills needed can all be mastered by a dedicated otologic surgeon.

Wireless, Fully Implantable and Expandable Electronic System for Bidirectional Electrical Neuromodulation of the Urinary Bladder.

Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladder─the inability to release urine naturally─include the use of medications, voiding techniques, and intermittent catheterization, for which the patient inserts a tube directly into the urethra to eliminate urine. Although those are life-saving techniques, there are still unfavorable side effects, including urinary tract infection (UTI), urethritis, irritation, and discomfort. Here, we report a wireless, fully implantable, and expandable electronic complex that enables elaborate management of abnormal bladder function via seamless integrations with the urinary bladder. Such electronics can not only record multiple physiological parameters simultaneously but also provide direct electrical stimulation based on a feedback control system. Uniform distribution of multiple stimulation electrodes via mesh-type geometry realizes low-impedance characteristics, which improves voiding/urination efficiency at the desired times. In vivo evaluations using live, free-moving animal models demonstrate system-level functionality.

Long-Term Follow-Up of the Auditory Threshold After a Fully Implantable Middle Ear Implant.

A fully implantable active middle ear device has been proposed and indicated for the rehabilitation of bilateral moderate or moderate-to-severe sensorineural hearing loss, assuming it would overcome the disadvantages of a conventional hearing aid. The indications have further been extended to severe or severe-to-profound forms of hearing loss in the case of an expected limited or null efficacy of hearing aids. While the literature has highlighted several positive aspects of the device, including a better quality of life related to its invisibility, the improvement of auditory and perceptual functions has not been controlled for throughout a long period of follow-up. The present study aimed to verify the behavior of the auditory threshold, especially the bone conduction (BC) component, in the implanted ear in a group of implantees affected by initial bilateral symmetric hearing loss of different severity grades. The BC threshold was assessed preoperatively at activation and at the last follow-up (ranging from 4 to 12 years) in the implanted ear, and preoperatively and at the last follow-up in the contralateral ear, to monitor eventual deteriorated values in both ears over time. The pure tone average (PTA; 250-4,000 Hz), speech reception threshold (SRT) and the maximum word recognition score as a percentage (% WRS) and in dB HL were measured in the implanted ear to verify the efficacy of the device after the first fitting at device activation. A significant worsening of the BC threshold with respect to the baseline threshold was noticed during further follow-up. When comparing the implanted ear with the contralateral ear, a significant worsening of the bone PTA was assessed in the former with respect to the contralateral ear. Despite the worsened hearing found in the implanted ears, the beneficial gains in PTA and speech audiometry observed at the first activation remained constant at the follow-up, thus showing an extension of the efficacy of this device in aiding those with up to the most severe forms of sensorineural hearing loss.

Oscillation Characteristics of an Artificial Cochlear Sensory Epithelium Optimized for a Micrometer-Scale Curved Structure.

Based on the modern microelectromechanical systems technology, we present a revolutionary miniaturized artificial cochlear sensory epithelium for future implantation tests on guinea pigs. The device was curved to fit the spiral structure of the cochlea and miniaturized to a maximum dimension of <1 mm to be implanted in the cochlea. First, the effect of the curved configuration on the oscillation characteristics of a trapezoidal membrane was evaluated using the relatively larger devices, which had a trapezoidal and a comparable curved shape designed for high-precision in vitro measurements. Both experimental and numerical analyses were used to determine the resonance frequencies and positions, and multiple oscillation modes were clearly observed. Because the maximum oscillation amplitude positions, i.e., the resonance positions, differed depending on the resonance frequencies in both trapezoidal and curved membrane devices, the sound frequency was determined based on the resonance position, thus reproducing the frequency selectivity of the basilar membrane in the organ of Corti. Furthermore, the resonance frequencies and positions of these two devices with different configurations were determined to be quantitatively consistent and similar in terms of mechanical dynamics. This result shows that despite a curved angle of 50−60°, the effect of the curved shape on oscillation characteristics was negligible. Second, the nanometer-scale oscillation of the miniaturized device was successfully measured, and the local resonance frequency in air was varied from 157 to 277 kHz using an experimental system that could measure the amplitude distribution in a two-dimensional (2D) plane with a high accuracy and reproducibility at a high speed. The miniaturized device developed in this study was shown to have frequency selectivity, and when the device was implanted in the cochlea, it was expected to discriminate frequencies in the same manner as the basilar membrane in the biological system. This study established methods for fabricating and evaluating the miniaturized device, and the proposed miniaturized device in a curved shape demonstrated the feasibility of next-generation cochlear implants.

Mathematical model of the auditory nerve response to stimulation by a micro-machined cochlea.

We report a novel mathematical model of an artificial auditory system consisting of a micro-machined cochlea and the auditory nerve response it evokes. The modeled micro-machined cochlea is one previously realized experimentally by mimicking functions of the cochlea [Shintaku et al, Sens. Actuat. 158 (2010) 183-192; Inaoka et al, Proc. Natl. Acad. Sci. USA 108 (2011) 18390-18395]. First, from the viewpoint of mechanical engineering, the frequency characteristics of a model device were experimentally investigated to develop an artificial basilar membrane based on a spring-mass-damper system. In addition, a nonlinear feedback controller mimicking the function of the outer hair cells was incorporated in this experimental system. That is, the developed device reproduces the proportional relationship between the oscillation amplitude of the basilar membrane and the cube root of the sound pressure observed in the mammalian auditory system, which is what enables it to have a wide dynamic range, and the characteristics of the control performance were evaluated numerically and experimentally. Furthermore, the stimulation of the auditory nerve by the micro-machined cochlea was investigated using the present mathematical model, and the simulation results were compared with our previous experimental results from animal testing [Shintaku et al, J. Biomech. Sci. Eng. 8 (2013) 198-208]. The simulation results were found to be in reasonably good agreement with those from the previous animal test; namely, there exists a threshold at which the excitation of the nerve starts and a saturation value for the firing rate under a large input. The proposed numerical model was able to qualitatively reproduce the results of the animal test with the micro-machined cochlea and is thus expected to guide the evaluation of micro-machined cochleae for future animal experiments.

The software defined implantable modular platform (STELLA) for preclinical deep brain stimulation research in rodents.

Context.Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals' behavior.Objective.To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models.Approach.We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6µA/3.1 V combined with an epoxy resin-based encapsulation method.Main results.STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. Whilein vitrostudies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA.Significance.We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to 'The Principle of Humane Experimental Technique'-replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.

Closing the Loop With Cortical Sensing: The Development of Adaptive Deep Brain Stimulation for Essential Tremor Using the Activa PC+S.

Deep Brain Stimulation (DBS) is an important tool in the treatment of pharmacologically resistant neurological movement disorders such as essential tremor (ET) and Parkinson's disease (PD). However, the open-loop design of current systems may be holding back the true potential of invasive neuromodulation. In the last decade we have seen an explosion of activity in the use of feedback to "close the loop" on neuromodulation in the form of adaptive DBS (aDBS) systems that can respond to the patient's therapeutic needs. In this paper we summarize the accomplishments of a 5-year study at the University of Washington in the use of neural feedback from an electrocorticography strip placed over the sensorimotor cortex. We document our progress from an initial proof of hardware all the way to a fully implanted adaptive stimulation system that leverages machine-learning approaches to simplify the programming process. In certain cases, our systems out-performed current open-loop approaches in both power consumption and symptom suppression. Throughout this effort, we collaborated with neuroethicists to capture patient experiences and take them into account whilst developing ethical aDBS approaches. Based on our results we identify several key areas for future work. "Graded" aDBS will allow the system to smoothly tune the stimulation level to symptom severity, and frequent automatic calibration of the algorithm will allow aDBS to adapt to the time-varying dynamics of the disease without additional input from a clinician. Additionally, robust computational models of the pathophysiology of ET will allow stimulation to be optimized to the nuances of an individual patient's symptoms. We also outline the unique advantages of using cortical electrodes for control and the remaining hardware limitations that need to be overcome to facilitate further development in this field. Over the course of this study we have verified the potential of fully-implanted, cortically driven aDBS as a feasibly translatable treatment for pharmacologically resistant ET.

Implementation of a fully implantable middle-ear hearing device chip.

BACKGROUND AND OBJECTIVE: Recently, with the increase in the population of hearing impaired people, various types of hearing aids have been rapidly developed. In particular, a fully implantable middle ear hearing device (F-IMEHD) is developed for people with sensorineural hearing loss. The F-IMEHD system comprises an implantable microphone, a transducer, and a signal processor. The signal processor should have a small size and consume less power for implantation in a human body. METHODS: In this study, we designed and fabricated a signal-processing chip using the modified FFT algorithm. This algorithm was developed focusing on eliminating time delay and system complexity in the transform process. The designed signal-processing chip comprises a 4-channel WDRC, a fitting memory, a communication 1control part, and a pulse density modulator. Each channel is separated using a 64-point fast Fourier transform (FFT) method and the gain value is matched using the fitting table in the fitting memory. RESULTS AND CONCLUSION: The chip was designed by Verilog-HDL and the designed HDL codes were verified by Modelsim-PE 10.3 (Mentor graphics, USA). The chip was fabricated using a 0.18 µm CMOS process (SMIC, China). Experiments were performed on a cadaver to verify the performance of the fabricated chip.

In-situ sensitivity of a totally-implantable microphone.

One of the key components of fully-implantable hearing devices is the implantable microphone. A crucial parameter when characterizing implantable microphones is the acoustic sensitivity, as it is one of the input parameters for the fitting algorithm and influences the achievable gain. The aim of our study was to investigate the sensitivity of an implanted subcutaneous microphone over time to answer two research questions: (1) How does the sensitivity change once the microphone is implanted under the skin (pre-op versus in-situ)? and (2) How does the sensitivity change from short-term to mid-term? We have measured the in-situ microphone sensitivity in three subjects implanted with a fully-implantable active middle ear implant from 2 weeks up to 20 weeks after implantation with a research software. The microphone sensitivity changed after implantation with clinically relevant changes around the resonance frequency of the microphone. Based on our results, it is essential to measure the in-situ microphone sensitivity at the time of initial fitting of the implant. Once implanted no clinically relevant changes in the microphone sensitivity were observed over time, with a clear decrease in variability over time.

A Preliminary Prototype High-Speed Feedback Control of an Artificial Cochlear Sensory Epithelium Mimicking Function of Outer Hair Cells.

A novel feedback control technique for the local oscillation amplitude in an artificial cochlear sensory epithelium that mimics the functions of the outer hair cells in the cochlea is successfully developed and can be implemented with a control time on the order of hundreds of milliseconds. The prototype artificial cochlear sensory epithelium was improved from that developed in our previous study to enable the instantaneous determination of the local resonance position based on the electrical output from a bimorph piezoelectric membrane. The device contains local patterned electrodes deposited with micro electro mechanical system (MEMS) technology that is used to detect the electrical output and oscillate the device by applying local electrical stimuli. The main feature of the present feedback control system is the principle that the resonance position is recognized by simultaneously measuring the local electrical outputs of all of the electrodes and comparing their magnitudes, which drastically reduces the feedback control time. In this way, it takes 0.8 s to control the local oscillation of the device, representing the speed of control with the order of one hundred times relative to that in the previous study using the mechanical automatic stage to scan the oscillation amplitude at each electrode. Furthermore, the intrinsic difficulties in the experiment such as the electrical measurement against the electromagnetic noise, adhesion of materials, and fatigue failure mechanism of the oscillation system are also shown and discussed in detail based on the many scientific aspects. The basic knowledge of the MEMS fabrication and the experimental measurement would provide useful suggestions for future research. The proposed preliminary prototype high-speed feedback control can aid in the future development of fully implantable cochlear implants with a wider dynamic range.

A microelectromechanical system (MEMS) capacitive accelerometer-based microphone with enhanced sensitivity for fully implantable hearing aid: a novel analytical approach.

The present work proposes a novel, compact, intuitively simple and efficient structure to improve the sensitivity of a microelectromechanical system (MEMS) capacitive accelerometer using an arrangement of microlever as a displacement amplifier. The accelerometer is proposed to serve as a microphone in the fully implantable cochlear prosthetic system which can be surgically implanted at the middle ear bone structure. Therefore, the design parameters such as size, weight and resonant frequency require deliberation. The paper presents a novel analytical model considering the impact of the mechanical amplification along with the width of the microlever and the capacitive fringe effects on the performance of the sensor. The design is simulated and verified using COMSOL MULTIPHYSICS 4.2. The accelerometer is designed within a sensing area of 1 mm2 and accomplishes a nominal capacitance of 4.85 pF and an excellent sensitivity of 5.91 fF/g.

First human use of a wireless coplanar energy transfer coupled with a continuous-flow left ventricular assist device.

The drive-line to power contemporary ventricular assist devices exiting the skin is associated with infection, and requires a holstered performance of the cardiac pump, which reduces overall quality of life. Attempts to eliminate the drive-line using transcutaneous energy transfer systems have been explored but have not succeeded in viable widespread application. The unique engineering of the coplanar energy transfer system is characterized by 2 large rings utilizing a coil-within-the-coil topology, ensuring robust resonance energy transfer while allowing for a substantial (>6 hours) unholstered circulatory support powered by an implantable battery source. Herein we report the first known human experience with this novel technology, coupled with a continuous-flow assist left ventricular assist device, in 2 consecutive patients evaluated with the primary end-point of system performance at 30 days post-implantation.

Totally Implantable Active Middle Ear Implants.

The Envoy Esteem and the Carina system are the 2 totally implantable hearing devices. The Esteem is designed for patients with bilateral moderate to severe sensorineural hearing loss who have an unaided speech discrimination score of greater than and equal to 40%. The Carina system is designed for patients with moderate to severe sensorineural hearing loss or those with mixed hearing loss. The Esteem offers a technologically advanced method to provide improvements in hearing and is available in the United States, whereas the Carina system is currently not available in the United States.

Ten years of active middle ear implantation for sensorineural hearing loss.

OBJECTIVES: To evaluate long-term benefits of a totally implantable active middle ear implant (AMEI) that has been used in a single implanting center for over 10 years. METHODS: Forty-one subjects who underwent implantation with an Esteem® AMEI during a 10-years period were evaluated on the auditory benefits, as derived from pure tone and speech audiometry tests. The analysis included a comparison with a conventional hearing aid, the problematics related to the battery duration and surgical replacement and, finally, the complication rate. RESULTS: Over 80% of the implanted subjects maintained over time a satisfactory auditory gain, ranging from 10 to over 30 dB in respect to the unaided situation, as mean at 0.5, 1, 2 and 4 kHz. In more than 60% of them, an improvement has also been found at 4 and 8 kHz. Battery duration varied according to the severity of the hearing loss and to the daily use of the device. No major post-operative complications were recorded, whilst explantation was necessary in five subjects, although none for device failure. CONCLUSIONS: The Esteem® can be considered a reliable device for rehabilitation of sensorineural hearing loss in alternative to conventional hearing aids.