Stretchable, Fully Polymeric Electrode Arrays for Peripheral Nerve Stimulation.

There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre-curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state-of-the-art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment.

Low-level light therapy using a helmet-type device for the treatment of androgenetic alopecia: A 16-week, multicenter, randomized, double-blind, sham device-controlled trial.

INTRODUCTION: Androgenetic alopecia is the most common form of hair loss in both sexes. In recent studies, low-level light therapy (LLLT) has been established as an effective treatment for alopecia. The purpose of this study was to evaluate the safety and efficacy of LLLT using a new helmet-type device for the treatment of androgenetic alopecia. METHOD: A randomized, sham device-controlled, double-blind clinical trial was conducted at 2 institutions. Sixty participants diagnosed with androgenetic alopecia aged from 19 to 65 years were recruited. LLLT was performed through a helmet-type device that emitted light with a mean output power of 2.36 mW/cm at a wavelength of 655 nm. Participants were divided into 2 groups, which respectively used the experimental device and a sham device. After tattooing at the central point of the vertex, phototrichograms at that point were obtained at 0, 8, and 16 weeks. The primary endpoint of the study was the difference in the rate of change of hair density between the test group and the control group. RESULTS: Comparing the results at baseline and week 16, the experimental group showed an increase in hair density of 41.90 hairs/cm and an increase in hair thickness of 7.50 µm, whereas the control group showed an increase of 0.72 hairs/cm and a decrease of 15.03 µm, respectively (P < .001). No adverse events or side effects occurred. CONCLUSION: LLLT showed a significant effect on increasing hair density in patients with androgenetic alopecia. LLLT could be a safe and effective treatment for androgenetic alopecia in both sexes.

Fabrication and characterization of polyimide-based 'smooth' titanium nitride microelectrode arrays for neural stimulation and recording.

OBJECTIVE: As electrodes are required to interact with sub-millimeter neural structures, innovative microfabrication processes are required to enable fabrication of microdevices involved in such stimulation and/or recording. This requires the development of highly integrated and miniaturized systems, comprising die-integration-compatible technology and flexible microelectrodes. To elicit selective stimulation and recordings of sub-neural structures, such microfabrication process flow can beneficiate from the integration of titanium nitride (TiN) microelectrodes onto a polyimide substrate. Finally, assembling onto cuffs is required, as well as electrode characterization. APPROACH: Flexible TiN microelectrode array integration and miniaturization was achieved through microfabrication technology based on microelectromechanical systems (MEMS) and complementary metal-oxide semiconductor processing techniques and materials. They are highly reproducible processes, granting extreme control over the feature size and shape, as well as enabling the integration of on-chip electronics. This design is intended to enhance the integration of future electronic modules, with high gains on device miniaturization. MAIN RESULTS: (a) Fabrication of two electrode designs, (1) 2 mm long array with 14 TiN square-shaped microelectrodes (80 × 80 µm2), and (2) an electrode array with 2 mm × 80 µm contacts. The average impedances at 1 kHz were 59 and 5.5 kΩ, respectively, for the smaller and larger contacts. Both designs were patterned on a flexible substrate and directly interconnected with a silicon chip. (b) Integration of flexible microelectrode array onto a cuff electrode designed for acute stimulation of the sub-millimeter nerves. (c) The TiN electrodes exhibited capacitive charge transfer, a water window of -0.6 V to 0.8 V, and a maximum charge injection capacity of 154 ± 16 µC cm-2. SIGNIFICANCE: We present the concept, fabrication and characterization of composite and flexible cuff electrodes, compatible with post-processing and MEMS packaging technologies, which allow for compact integration with control, readout and RF electronics. The fabricated TiN microelectrodes were electrochemically characterized and exhibited a comparable performance to other state-of-the-art electrodes for neural stimulation and recording. Therefore, the presented TiN-on-polyimide microelectrodes, released from silicon wafers, are a promising solution for neural interfaces targeted at sub-millimeter nerves, which may benefit from future upgrades with die-electronic modules.

Recommendation of New Medical Alarms Based on Audibility, Identifiability, and Detectability in a Randomized, Simulation-Based Study.

OBJECTIVES: Accurate and timely identification of existing audible medical alarms is not adequate in clinical settings. New alarms that are easily heard, quickly identifiable, and discernable from one another are indicated. The "auditory icons" (brief sounds that serve as metaphors for the events they represent) have been proposed as a replacement to the current international standard. The objective was to identify the best performing icons based on audibility and performance in a simulated clinical environment. DESIGN: Three sets of icon alarms were designed using empirical methods. Subjects participated in a series of clinical simulation experiments that examined the audibility, identification accuracy, and response time of each of these icon alarms. A statistical model that combined the outcomes was used to rank the alarms in overall efficacy. We constructed the "best" and "worst" performing sets based on this ranking and prospectively validated these sets in a subsequent experiment with a new subject sample. SETTING: Experiments were conducted in simulated ICU settings at the University of Miami. SUBJECTS: Medical trainees were recruited from a convenience sample of nursing students and anesthesia residents at the institution. INTERVENTIONS: In Experiment 1 (formative testing), subjects were exposed to one of the three sets of alarms; identical setting and instruments were used throughout. In Experiment 2 (summative testing), subjects were exposed to one of the two sets of alarms, assembled from the best and worst performing alarms from Experiment 1. MEASUREMENTS AND MAIN RESULTS: For each alarm, we determined the minimum sound level to reach audibility threshold in the presence of background clinical noise, identification accuracy (percentage), and response time (seconds). We enrolled 123 medical trainees and professionals for participation (78 with < 6 yr of training). We identified the best performing icon alarms for each category, which matched or exceeded the other candidate alarms in identification accuracy and response time. CONCLUSIONS: We propose a set of eight auditory icon alarms that were selected through formative testing and validated through summative testing for adoption by relevant regulatory bodies and medical device manufacturers.

A study of reproducibility of kinesiology tape applications: review, reliability and validity.

BACKGROUND: Literature addressing the mechanical properties of kinesiology tape is quite scarce. There are no studies which focus on the mechanical characteristics of kinesiology tape, its mechanical properties, nor its adherence following the ISO international standard test methods for tape elongation. METHODS: This study quantified the mechanical characteristics of 380 samples of kinesiology tape from 19 different brands and in 4 different colors using a dynamometer. Mechanical testing was controlled by UNE EN ISO 13934-1. RESULTS: Significant differences were found between tape brands in terms of grammage, maximum force tenacity, work, pre-elongation and percentage elongation (P < .001). Regarding kinesiology tape color, statistically significant differences were found between tape brands in terms of grammage, maximum force and tenacity (P < .001), work and pre-elongation (P < .05). When adherence was studied, statistically significant differences were found between tape brands in terms of maximum force and work (P < .001). CONCLUSIONS: The different kinesiology tapes presented different behaviors with regard to rupture and removal when applied to skin in dry state, wet state and after being submerged in artificial acidic sweat solution. Therefore, different kinesiology tape brands will produce different levels of strain even though the same elongation is used. Depending on the characteristics (body dimensions) and properties (skin elongation) of each subject in the sample, bandages with different elongations must be applied to achieve the same strain in all of the tapes and therefore produce the same effect. The absence of these data at this time limits the reliability of previous clinical studies, makes comparing their findings impossible and presents new challenges for research in this field.

Thrust force characterization of free-swimming soft robotic jellyfish.

Five unique soft robotic jellyfish were manufactured with eight pneumatic network tentacle actuators extending radially from their centers. These jellyfish robots were able to freely swim untethered in the ocean, to steer from side to side, and to swim through orifices more narrow than the nominal diameter of the jellyfish. Each of the five jellyfish robots were manufactured with a different composition of body and tentacle actuator Shore hardness. A three-factor study was performed with these five jellyfish robots to determine the impact that actuator material Shore hardness, actuation frequency, and tentacle stroke actuation amplitude had upon the measured thrust force. It was found that all three of these factors significantly impacted mean thrust force generation, which peaked with a half-stroke actuation amplitude at a frequency of 0.8 Hz.

Comparison of the performance of battery-operated fluid warmers.

OBJECTIVES: Warming intravenous fluids is essential to prevent hypothermia in patients with trauma, especially when large volumes are administered. Prehospital and transport settings require fluid warmers to be small, energy efficient and independent of external power supply. We compared the warming properties and resistance to flow of currently available battery-operated fluid warmers. METHODS: Fluid warming was evaluated at 50, 100 and 200 mL/min at a constant input temperature of 20°C and 10°C using a cardiopulmonary bypass roller pump and cooler. Output temperature was continuously recorded. RESULTS: Performance of fluid warmers varied with flows and input temperatures. At an input temperature of 20°C and flow of 50 mL/min, the Buddy Lite, enFlow, Thermal Angel and Warrior warmed 3.4, 2.4, 1 and 3.6 L to over 35°C, respectively. However, at an input temperature of 10°C and flow of 200 mL/min, the Buddy Lite failed to warm, the enFlow warmed 3.3 L to 25.7°C, the Thermal Angel warmed 1.5 L to 20.9°C and the Warrior warmed 3.4 L to 34.4°C (p<0.0001). CONCLUSION: We found significant differences between the fluid warmers: the use of the Buddy Lite should be limited to moderate input temperature and low flow rates. The use of the Thermal Angel is limited to low volumes due to battery capacity and low output temperature at extreme conditions. The Warrior provides the best warming performance at high infusion rates, as well as low input temperatures, and was able to warm the largest volumes in these conditions.

Development of new hard hat dimensions using user-centered design approach among oil palm harvesters.

BACKGROUND: Hard hats are among the personal protective equipment (PPE) used in many industries to reduce the impact of any falling object on the skull and also to prevent head and brain injuries. However, the practice of wearing a safety helmet during working hours is still low. This is due to the physical discomfort perceived by safety helmet users. OBJECTIVE: Given the unpopularity of the current hard hat, the general perception of workers concerning its use and its measurements are the determining factors in the development of a new hard hat. METHOD: A cross-sectional study was conducted in which 132 male oil palm harvesters between 19 and 60 years of age were selected from among the employees of the same oil palm harvesting company. A set of questionnaires was developed to collect their socio-demographic information as well as their perceptions of comfort and the prevalence of head injury. In addition, a set of measuring instruments, including Martin's anthropometry set, was used for head measurement and data collection in respect of the current hard hat. In this research, six respondents were randomly selected to attend an interview session for qualitative assessment.RESULTSBased on the questionnaires, the unpopularity in the use of the hard hat was largely influenced by factors related to poor design, in general, and, specifically, poor ventilation (64%), load (67% ), and physical discomfort (42% ). The measurements of the anthropometric parameters and the dimensions of the hard hat also showed a significant mismatch. CONCLUSION: The unpopularity of the current hard hat among oil palm harvesters stemmed from the discomfort from wearing, which showed that the development of a new hard hat could lead to better usage and the greater likelihood of wearing a hard hat throughout the working day.

Assistive technology and people: a position paper from the first global research, innovation and education on assistive technology (GREAT) summit.

Assistive technology (AT) is a powerful enabler of participation. The World Health Organization's Global Collaboration on Assistive Technology (GATE) programme is actively working towards access to assistive technology for all. Developed through collaborative work as a part of the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit, this position paper provides a "state of the science" view of AT users, conceptualized as "People" within the set of GATE strategic "P"s. People are at the core of policy, products, personnel and provision. AT is an interface between the person and the life they would like to lead. People's preferences, perspectives and goals are fundamental to defining and determining the success of AT. Maximizing the impact of AT in enabling participation requires an individualized and holistic understanding of the value and meaning of AT for the individual, taking a universal model perspective, focusing on the person, in context, and then considering the condition and/or the technology. This paper aims to situate and emphasize people at the centre of AT systems: we highlight personal meanings and perspectives on AT use and consider the role of advocacy, empowerment and co-design in developing and driving AT processes.

Automatic application of neural stimulation during wheelchair propulsion after SCI enhances recovery of upright sitting from destabilizing events.

BACKGROUND: The leading cause of injury for manual wheelchair users are tips and falls caused by unexpected destabilizing events encountered during everyday activities. The purpose of this study was to determine the feasibility of automatically restoring seated stability to manual wheelchair users with spinal cord injury (SCI) via a threshold-based system to activate the hip and trunk muscles with electrical stimulation during potentially destabilizing events. METHODS: We detected and classified potentially destabilizing sudden stops and turns with a wheelchair-mounted wireless inertial measurement unit (IMU), and then applied neural stimulation to activate the appropriate muscles to resist trunk movement and restore seated stability. After modeling and preliminary testing to determine the appropriate inertial signatures to discriminate between events and reliably trigger stimulation, the system was implemented and evaluated in real-time on manual wheelchair users with SCI. Three participants completed simulated collision events and four participants completed simulated rapid turns. Data were analyzed as a series of individual case studies with subjects acting as their own controls with and without the system active. RESULTS: The controller achieved 93% accuracy in detecting collisions and right turns, and 100% accuracy in left turn detection. Two of the three subjects who participated in collision testing with stimulation experienced significantly decreased maximum anterior-posterior trunk angles (p < 0.05). Similar results were obtained with implanted and surface stimulation systems. CONCLUSIONS: This study demonstrates the feasibility of a neural stimulation control system based on simple inertial measurements to improve trunk stability and overall safety of people with spinal cord injuries during manual wheelchair propulsion. Further studies are required to determine clinical utility in real world situations and generalizability to the broader SCI or other population of manual or powered wheelchair users. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01474148 . Registered 11/08/2011 retrospectively registered.

DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 2 - Ocular DynaMiTES for drug absorption studies of the anterior eye.

In the present study, a formerly designed Dynamic Micro Tissue Engineering System (DynaMiTES) was applied with our prevalidated human hemicornea (HC) construct to obtain a test platform for improved absorption studies of the anterior eye (Ocular DynaMiTES). First, the cultivation procedure of the classic HC was slightly adapted to the novel DynaMiTES design. The obtained inverted HC was then compared to classic HC regarding cell morphology using light and scanning electron microscopy, cell viability using MTT dye reaction and epithelial barrier properties observing transepithelial electrical resistance and apparent permeation coefficient of sodium fluorescein. These tested cell criteria were similar. In addition, the effects of four different flow rates on the same cell characteristics were investigated using the DynaMiTES. Because no harmful potential of flow was found, dynamic absorption studies of sodium fluorescein with and without 0.005%, 0.01% and 0.02% benzalkonium chloride were performed compared to the common static test procedure. In this proof-of-concept study, the dynamic test conditions showed different results than the static test conditions with a better prediction of in vivo data. Thus, we propose that our DynaMiTES platform provides great opportunities for the improvement of common in vitro drug testing procedures.

DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 1 - Engineering of microfluidic system and technical simulations.

Conventional safety and efficacy test models, such as animal experiments or static in vitro cell culture models, can often not reliably predict the most promising drug candidates. Therefore, a novel microfluidic cell culture platform, called Dynamic Micro Tissue Engineering System (DynaMiTES), was designed to allow online analysis of drugs permeating through barrier forming tissues under dynamic conditions combined with monitoring of the transepithelial electrical resistance (TEER) by electrodes optimized for homogeneous current distribution. A variety of pre-cultivated cell culture inserts can be integrated and exposed to well controlled dynamic micro flow conditions, resulting in a tightly regulated exposure of the cells to tested drugs, drug formulations and shear forces. With these qualities, the new system can provide more relevant information compared to static measurements. As a first in vitro model, a three-dimensional hemicornea construct consisting of human keratocytes (HCK-Ca) and epithelial cells (HCE-T) was successfully tested in the DynaMiTES. Thereby, we were able to demonstrate the functionality and cell compatibility of this new organ on chip test platform. The modular design of the DynaMiTES allows fast adaptation suitable for the investigation of drug permeation through other important cellular barriers.

A novel three-dimensional printed guiding device for electrode implantation of sacral neuromodulation.

AIM: The aim was to test the feasibility of a novel three-dimensional (3D) printed guiding device for electrode implantation of sacral neuromodulation (SNM). METHOD: A 3D printed guiding device for electrode implantation was customized to patients' anatomy of the sacral region. Liquid photopolymer was selected as the printing material. The details of the device designation and prototype building are described. The guiding device was used in two patients who underwent SNM for intractable constipation. Details of the procedure and the outcomes are given. RESULTS: With the help of the device, the test needle for stimulation was placed in the target sacral foramen successfully at the first attempt of puncture in both patients. The time to implant a tined SNM electrode was less than 20 min and no complications were observed. At the end of the screening phase, symptoms of constipation were relieved by more than 50% in both patients and permanent stimulation was established. CONCLUSION: The customized 3D printed guiding device for implantation of SNM is a promising instrument that facilitates a precise and quick implantation of the electrode into the target sacral foramen.

Designing, Prototyping and Evaluating Digital Mindfulness Applications: A Case Study of Mindful Breathing for Stress Reduction.

BACKGROUND: During the past decade, there has been a rapid increase of interactive apps designed for health and well-being. Yet, little research has been published on developing frameworks for design and evaluation of digital mindfulness facilitating technologies. Moreover, many existing digital mindfulness applications are purely software based. There is room for further exploration and assessment of designs that make more use of physical qualities of artifacts. OBJECTIVE: The study aimed to develop and test a new physical digital mindfulness prototype designed for stress reduction. METHODS: In this case study, we designed, developed, and evaluated HU, a physical digital mindfulness prototype designed for stress reduction. In the first phase, we used vapor and light to support mindful breathing and invited 25 participants through snowball sampling to test HU. In the second phase, we added sonification. We deployed a package of probes such as photos, diaries, and cards to collect data from users who explored HU in their homes. Thereafter, we evaluated our installation using both self-assessed stress levels and heart rate (HR) and heart rate variability (HRV) measures in a pilot study, in order to measure stress resilience effects. After the experiment, we performed a semistructured interview to reflect on HU and investigate the design of digital mindfulness apps for stress reduction. RESULTS: The results of the first phase showed that 22 of 25 participants (88%) claimed vapor and light could be effective ways of promoting mindful breathing. Vapor could potentially support mindful breathing better than light (especially for mindfulness beginners). In addition, a majority of the participants mentioned sound as an alternative medium. In the second phase, we found that participants thought that HU could work well for stress reduction. We compared the effect of silent HU (using light and vapor without sound) and sonified HU on 5 participants. Subjective stress levels were statistically improved with both silent and sonified HU. The mean value of HR using silent HU was significantly lower than resting baseline and sonified HU. The mean value of root mean square of differences (RMSSD) using silent HU was significantly higher than resting baseline. We found that the differences between our objective and subjective assessments were intriguing and prompted us to investigate them further. CONCLUSIONS: Our evaluation of HU indicated that HU could facilitate relaxed breathing and stress reduction. There was a difference in outcome between the physiological measures of stress and the subjective reports of stress, as well as a large intervariability among study participants. Our conclusion is that the use of stress reduction tools should be customized and that the design work of mindfulness technology for stress reduction is a complex process, which requires cooperation of designers, HCI (Human-Computer Interaction) experts and clinicians.

An open source, wireless capable miniature microscope system.

OBJECTIVE: Fluorescence imaging through head-mounted microscopes in freely behaving animals is becoming a standard method to study neural circuit function. Flexible, open-source designs are needed to spur evolution of the method. APPROACH: We describe a miniature microscope for single-photon fluorescence imaging in freely behaving animals. The device is made from 3D printed parts and off-the-shelf components. These microscopes weigh less than 1.8 g, can be configured to image a variety of fluorophores, and can be used wirelessly or in conjunction with active commutators. Microscope control software, based in Swift for macOS, provides low-latency image processing capabilities for closed-loop, or BMI, experiments. MAIN RESULTS: Miniature microscopes were deployed in the songbird premotor region HVC (used as a proper name), in singing zebra finches. Individual neurons yield temporally precise patterns of calcium activity that are consistent over repeated renditions of song. Several cells were tracked over timescales of weeks and months, providing an opportunity to study learning related changes in HVC. SIGNIFICANCE: 3D printed miniature microscopes, composed completely of consumer grade components, are a cost-effective, modular option for head-mounting imaging. These easily constructed and customizable tools provide access to cell-type specific neural ensembles over timescales of weeks.

Principles for fostering the transdisciplinary development of assistive technologies.

Developing useful and usable assistive technologies often presents complex (or "wicked") challenges that require input from multiple disciplines and sectors. Transdisciplinary collaboration can enable holistic understanding of challenges that may lead to innovative, impactful and transformative solutions. This paper presents generalised principles that are intended to foster transdisciplinary assistive technology development. The paper introduces the area of assistive technology design before discussing general aspects of transdisciplinary collaboration followed by an overview of relevant concepts, including approaches, methodologies and frameworks for conducting and evaluating transdisciplinary working and assistive technology design. The principles for transdisciplinary development of assistive technologies are presented and applied post hoc to the COACH project, an ambient-assisted living technology for guiding completion of activities of daily living by older adults with dementia as an illustrative example. Future work includes the refinement and validation of these principles through their application to real-world transdisciplinary assistive technology projects. Implications for rehabilitation Transdisciplinarity encourages a focus on real world 'wicked' problems. A transdisciplinary approach involves transcending disciplinary boundaries and collaborating with interprofessional and community partners (including the technology's intended users) on a shared problem. Transdisciplinarity fosters new ways of thinking about and doing research, development, and implementation, expanding the scope, applicability, and commercial viability of assistive technologies.

A multiport MR-compatible neuroendoscope: spanning the gap between rigid and flexible scopes.

OBJECTIVE Rigid endoscopes enable minimally invasive access to the ventricular system; however, the operative field is limited to the instrument tip, necessitating rotation of the entire instrument and causing consequent tissue compression while reaching around corners. Although flexible endoscopes offer tip steerability to address this limitation, they are more difficult to control and provide fewer and smaller working channels. A middle ground between these instruments-a rigid endoscope that possesses multiple instrument ports (for example, one at the tip and one on the side)-is proposed in this article, and a prototype device is evaluated in the context of a third ventricular colloid cyst resection combined with septostomy. METHODS A prototype neuroendoscope was designed and fabricated to include 2 optical ports, one located at the instrument tip and one located laterally. Each optical port includes its own complementary metal-oxide semiconductor (CMOS) chip camera, light-emitting diode (LED) illumination, and working channels. The tip port incorporates a clear silicone optical window that provides 2 additional features. First, for enhanced safety during tool insertion, instruments can be initially seen inside the window before they extend from the scope tip. Second, the compliant tip can be pressed against tissue to enable visualization even in a blood-filled field. These capabilities were tested in fresh porcine brains. The image quality of the multiport endoscope was evaluated using test targets positioned at clinically relevant distances from each imaging port, comparing it with those of clinical rigid and flexible neuroendoscopes. Human cadaver testing was used to demonstrate third ventricular colloid cyst phantom resection through the tip port and a septostomy performed through the lateral port. To extend its utility in the treatment of periventricular tumors using MR-guided laser therapy, the device was designed to be MR compatible. Its functionality and compatibility inside a 3-T clinical scanner were also tested in a brain from a freshly euthanized female pig. RESULTS Testing in porcine brains confirmed the multiport endoscope's ability to visualize tissue in a blood-filled field and to operate inside a 3-T MRI scanner. Cadaver testing confirmed the device's utility in operating through both of its ports and performing combined third ventricular colloid cyst resection and septostomy with an endoscope rotation of less than 5°. CONCLUSIONS The proposed design provides freedom in selecting both the number and orientation of imaging and instrument ports, which can be customized for each ventricular pathological entity. The lightweight, easily manipulated device can provide added steerability while reducing the potential for the serious brain distortion that happens with rigid endoscope navigation. This capability would be particularly valuable in treating hydrocephalus, both primary and secondary (due to tumors, cysts, and so forth). Magnetic resonance compatibility can aid in endoscope-assisted ventricular aqueductal plasty and stenting, the management of multiloculated complex hydrocephalus, and postinflammatory hydrocephalus in which scarring obscures the ventricular anatomy.

Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates.

OBJECTIVE: Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. APPROACH: We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. MAIN RESULTS: SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. SIGNIFICANCE: These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes.

A CT-, PET- and MR-imaging-compatible hyperbaric pressure chamber for baromedical research.

OBJECTIVES: We describe the development of a novel preclinical rodent-sized pressure chamber system compatible with computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI) that allows continuous uncompromised and minimally invasive data acquisition throughout hyperbaric exposures. The effect of various pressures on the acquired image intensity obtained with different CT, PET and MRI phantoms are characterised. MATERIAL AND METHODS: Tissue-representative phantom models were examined with CT, PET or MRI at normobaric pressure and hyperbaric pressures up to 1.013 mPa. The relationships between the acquired image signals and pressure were evaluated by linear regression analysis for each phantom. RESULTS: CT and PET showed no effect of pressure per se, except for CT of air, demonstrating an increase in Hounsfield units in proportion to the pressure. For MRI, pressurisation induced no effect on the longitudinal relaxation rate (R1), whereas the transversal relaxation rate (R2) changed slightly. The R2 data further revealed an association between pressure and the concentration of the paramagnetic nuclei gadolinium, the contrast agent used to mimic different tissues in the MRI phantoms. CONCLUSION: This study demonstrates a pressure chamber system compatible with CT, PET and MRI. We found that no correction in image intensity was required with pressurisation up to 1.013 mPa for any imaging modality. CT, PET or MRI can be used to obtain anatomical and physiological information from pressurised model animals in this chamber.