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The major challenge in developing a wireless brain implant is to establish a stable and efficient trans‐cranial wireless link with an integrated implantable antenna. This chapter discusses the challenges in developing the intracranial implantable antennas and compares different techniques for wireless power transfer in the presence of human body tissues. It provides a summary of the most recent miniature implantable antennas and inductive power transfer systems for implantable applications. Next, the chapter compares the merits of different methodologies to build the computational head models for implantable antenna development. A comparison of the human head models with different complexity is provided. Then, the chapter discusses the development and the performance of a wirelessly powered intracranial pressure sensing system integrating near‐ and far‐field antennas in the human head environment. Two far‐field radio‐frequency identification antennas for intracranial wireless communication are demonstrated and evaluated. Finally, the chapter discusses the antenna performance and the tuning parameters through a parametric analysis.

Implantable neural devices are the most widely applied tools in neuroscience research as well as neuroprosthetics to record neural signal activities at single‐neuron and sub‐millisecond resolution. However, lack of mechanical compatibility between the traditional rigid probes and brain tissues causes neuroinflammatory responses and deteriorate recorded signal quality. Decreasing the cross‐sectional area while improving flexibility of the probes can significantly enhance the chronic stability of neural interfaces. Additionally, magnetic resonance imaging (MRI) compatibility is another issue that should be addressed for the development of future implantable devices. Herein, current advancement in developing the chronically stable implantable neural devices is highlighted, with a emphasis on making use of the sophisticated materials and structural design concepts.

The chronic reliability of bioelectronic neural interfaces has been challenged by foreign body reactions (FBRs) resulting in fibrotic encapsulation and poor integration with neural tissue. Engineered microtopographies could alleviate these challenges by manipulating cellular responses to the implanted device. Parallel microchannels have been shown to modulate neuronal cell alignment and axonal growth, and Sharklet™ microtopographies of targeted feature sizes can modulate bio-adhesion of an array of bacteria, marine organisms, and epithelial cells due to their unique geometry. We hypothesized that a Sharklet™ micropattern could be identified that inhibited fibroblasts partially responsible for FBR while promoting Schwann cell proliferation and alignment. in vitro cell assays were used to screen the effect of Sharklet™ and channel micropatterns of varying dimensions from 2 to 20 μm on fibroblast and Schwann cell metrics (e.g., morphology/alignment, nuclei count, metabolic activity), and a hierarchical analysis of variance was used to compare treatments. In general, Schwann cells were found to be more metabolically active and aligned than fibroblasts when compared between the same pattern. 20 μm wide channels spaced 2 μm apart were found to promote Schwann cell attachment and alignment while simultaneously inhibiting fibroblasts and warrant further in vivo study on neural interface devices. No statistically significant trends between cellular responses and geometrical parameters were identified because mammalian cells can change their morphology dependent on their environment in a manner dissimilar to bacteria. Our results showed although surface patterning is a strong physical tool for modulating cell behavior, responses to micropatterns are highly dependent on the cell type., Defense Advanced Research Projects Agency, Grant/Award Number: HR0011-15-2-0030

Neurological diseases are a prevalent cause of global mortality and are of growing concern when considering an ageing global population. Traditional treatments are accompanied by serious side effects including repeated treatment sessions, invasive surgeries, or infections. For example, in the case of deep brain stimulation, large, stiff, and battery powered neural probes recruit thousands of neurons with each pulse, and can invoke a vigorous immune response. This paper presents challenges in engineering and neuroscience in developing miniaturized and biointegrated alternatives, in the form of microelectrode probes. Progress in design and topology of neural implants has shifted the goal post toward highly specific recording and stimulation, targeting small groups of neurons and reducing the foreign body response with biomimetic design principles. Implantable device design recommendations, fabrication techniques, and clinical evaluation of the impact flexible, integrated probes will have on the treatment of neurological disorders are provided in this report. The choice of biocompatible material dictates fabrication techniques as novel methods reduce the complexity of manufacture. Wireless power, the final hurdle to truly implantable neural interfaces, is discussed. These aspects are the driving force behind continued research: significant breakthroughs in any one of these areas will revolutionize the treatment of neurological disorders., In this progress report, the evolution of neural stimulation is explored with a view to providing practical design guidelines for innovative, flexible, and fully integrated implantable probes. From the foreign body response, to the material characteristics of the brain, all aspects of the target tissue must be accommodated. Fabrication techniques, as well as wireless power approaches, are also discussed.

The long-term application of central nervous system implants is currently limited by the negative response of the brain tissue, affecting both the performance of the device and the survival of nearby cells. Topographical modification of implant surfaces mimicking the structure and dimensions of the extracellular matrix may provide a solution to this negative tissue response and has been shown to affect the attachment and behavior of both neurons and astrocytes. In our study, commonly used neural implant materials, silicon, and platinum were tested with or without nanoscale surface modifications. No biological coatings were used in order to only examine the effect of the nanostructuring. We seeded primary mouse astrocytes and hippocampal neurons onto four different surfaces: flat polysilicon, nanostructured polysilicon, and platinum-coated versions of these surfaces. Fluorescent wide-field, confocal, and scanning electron microscopy were used to characterize the attachment, spreading and proliferation of these cell types. In case of astrocytes, we found that both cell number and average cell spreading was significantly larger on platinum, compared to silicon surfaces, while silicon surfaces impeded glial proliferation. Nanostructuring did not have a significant effect on either parameter in astrocytes but influenced the orientation of actin filaments and glial fibrillary acidic protein fibers. Neuronal soma attachment was impaired on metal surfaces while nanostructuring seemed to influence neuronal growth cone morphology, regardless of surface material. Taken together, the type of metals tested had a profound influence on cellular responses, which was only slightly modified by nanopatterning.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter‐sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin‐film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin‐film conductor grids do not generate diagnostic‐impeding imaging artefacts (, Current clinical electrocorticography (ECoGs) grids are made from stiff materials and only offer sparse brain sampling during epilepsy or tumor surgeries. Here conformable ECoG grids made from silicone membranes permit easy implantation in hidden anatomical locations in cadaveric specimen and imaging compatibility with 3T magnetic resonance imaging. In vivo in a minipig model the conformable ECoG grids show high‐resolution brain recordings.

Author(s): Sahyouni, Ronald; Chang, David T; Moshtaghi, Omid; Mahmoodi, Amin; Djalilian, Hamid R; Lin, Harrison W | Abstract: Permanent injury to the cranial nerves can often result in a substantial reduction in quality of life. Novel and innovative interventions can help restore form and function in nerve paralysis, with bioelectric interfaces among the more promising of these approaches. The foreign body response is an important consideration for any bioelectric device as it influences the function and effectiveness of the implant. The purpose of this review is to describe tissue and functional effects of chronic neural implantation among the different categories of neural implants and highlight advances in peripheral and cranial nerve stimulation.Data Sources: PubMed, IEEE, and Web of Science literature search.Review Methods: A review of the current literature was conducted to examine functional and histologic effects of bioelectric interfaces for neural implants.Bioelectric devices can be characterized as intraneural, epineural, perineural, intranuclear, or cortical depending on their placement relative to nerves and neuronal cell bodies. Such devices include nerve-specific stimulators, neuroprosthetics, brainstem implants, and deep brain stimulators. Regardless of electrode location and interface type, acute and chronic histological, macroscopic and functional changes can occur as a result of both passive and active tissue responses to the bioelectric implant.A variety of chronically implantable electrodes have been developed to treat disorders of the peripheral and cranial nerves, to varying degrees of efficacy. Consideration and mitigation of detrimental effects at the neural interface with further optimization of functional nerve stimulation will facilitate the development of these technologies and translation to the clinic.3.

Neuroscience is an essential field of investigation that reveals the identity of human beings, with a comprehensive understanding of advanced mental activities, through the study of neurobiological structures and functions. Fully understanding the neurotransmission system that allows for connectivity among neuronal circuits has paved the way for the development of treatments for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and depression. The field of flexible implants has attracted increasing interest mainly to overcome the mechanical mismatch between rigid electrode materials and soft neural tissues, enabling precise measurements of neural signals from conformal contact. Here, the current issues of flexible neural implants (chronic device failure, non-bioresorbable electronics, low-density electrode arrays, among others are summarized) by presenting material candidates and designs to address each challenge. Furthermore, the latest investigations associated with the aforementioned issues are also introduced, including suggestions for ideal neural implants. In terms of the future direction of these advances, designing flexible devices would provide new opportunities for the study of brain-machine interfaces or brain-computer interfaces as part of locomotion through brain signals, and for the treatment of neurodegenerative diseases.

For brain computer interfaces (BCI), the immune response to implanted electrodes is a major biological cause of device failure. Bioactive coatings such as neural adhesion molecule L1 have been shown to improve the biocompatibility, but are difficult to handle or produce in batches. Here, a synthetic zwitterionic polymer coating, poly(sulfobetaine methacrylate) (PSBMA) is developed for neural implants with the goal of reducing the inflammatory host response. In tests in vitro, the zwitterionic coating inhibits protein adsorption and the attachment of fibroblasts and microglia, and remains stable for at least 4 weeks. In vivo two-photon microscopy on CX3CR1-GFP mice shows that the zwitterionic coating significantly suppresses the microglial encapsulation of neural microelectrodes over a 6 h observation period. Furthermore, the lower microglial encapsulation on zwitterionic polymer-coated microelectrodes is revealed to originate from a reduction in the size but not the number of microglial end feet. This work provides a facile method for coating neural implants with zwitterionic polymers and illustrates the initial interaction between microglia and coated surface at high temporal and spatial resolution.

The rapid pace of progress in implantable electronics driven by novel technology has created devices with unconventional designs and features to reduce invasiveness and establish new sensing and stimulating techniques. Among the designs, injectable forms of biomedical electronics are explored for accurate and safe targeting of deep-seated body organs. Here, the classes of biomedical electronics and tools that have high aspect ratio structures designed to be injected or inserted into internal organs for minimally invasive monitoring and therapy are reviewed. Compared with devices in bulky or planar formats, the long shaft-like forms of implantable devices are easily placed in the organs with minimized outward protrusions via injection or insertion processes. Adding flexibility to the devices also enables effortless insertions through complex biological cavities, such as the cochlea, and enhances chronic reliability by complying with natural body movements, such as the heartbeat. Diverse types of such injectable implants developed for different organs are reviewed and the electronic, optoelectronic, piezoelectric, and microfluidic devices that enable stimulations and measurements of site-specific regions in the body are discussed. Noninvasive penetration strategies to deliver the miniscule devices are also considered. Finally, the challenges and future directions associated with deep body biomedical electronics are explained.

Polymer‐derived carbon can serve as an electrode material in multimodal neural stimulation, recording, and neurotransmitter sensing platforms. The primary challenge in its applicability in implantable, flexible neural devices is its characteristic mechanical hardness that renders it difficult to fabricate the entire device using only carbon. A microfabrication technique is introduced for patterning flexible, cloth‐like, polymer‐derived carbon fiber (CF) mats embedded in polyimide (PI), via selective reactive ion etching. This scalable, monolithic manufacturing method eliminates any joints or metal interconnects and creates electrocorticography electrode arrays based on a single CF mat. The batch‐fabricated CF/PI composite structures, with critical dimension of 12.5 µm, are tested for their mechanical, electrical, and electrochemical stability, as well as to chemicals that mimic acute postsurgery inflammatory reactions. Their recording performance is validated in rat models. Reported CF patterning process can benefit various carbon microdevices that are expected to feature flexibility, material stability, and biocompatibility.

Cochlear implants restore the inner ear hearing using electrical stimulation of the auditory nerve. However, there is potential to improve the implant's function in terms of stimulation selectivity by increasing the number of electrode contacts. Meanwhile, the electrode stiffness shall not be elevated, because this would enhance insertion trauma and fibrous tissue encapsulation of the implant. Since the increase in the number of electrode contacts results in an increase of electrode stiffness, novel materials are needed for manufacturing electrode shafts. Carbon nanotubes (CNTs) as electrode contacts offer new perspectives concerning mechanical properties and electrode-nerve interfacing. However, by using CNTs immersed in liquid silicone rubber (LSR) as electrode material, the electrical conductivity of the bulk needs to be improved. The aim of this study was to investigate the potential of using CNT–LSR as electrode material by increasing the conductivity of such materials and confirming their biocompatibility. First results show, that the electrode material can be printed in isolated layers, while the conductivity of the bulk can be improved. Fibroblasts growth tests indicated biocompatible properties of CNT–LSR samples. In conclusion CNT–LSR materials can be considered as promising candidates for use in neural implants possessing proper mechanical, electrical as well as biocompatible properties.

Brain implants, such as Deep Brain Stimulation (DBS), which are designed to improve motor, mood and behavioural pathology, present unique challenges to our understanding of identity, agency and free will. This is because these devices can have visible effects on persons' physical and psychological properties yet are essentially undetectable when operating correctly. They can supplement and compensate for one's inherent abilities and faculties when they are compromised by neuropsychiatric disorders. Further, unlike talk therapy or pharmacological treatments, patients need not ‘do’ anything for the treatment to take effect. If one accepts, as we argue here, that brain implants are unique among implantable types of devices, then this can have significant implications for what it means to persist as the same person and be the source of one's thoughts and actions. By examining two of the most common indications for DBS in current use, namely in the motor (Parkinson's Disease) and psychiatric (Major Depression) domains, we further argue that although DBS, as it is currently applied, does not necessarily represent a unique threat to personal identity and agency per se, it introduces an unprecedented ‘third party’ into the debate on these concepts. In this way, DBS can be used as a tool to begin probing, both conceptually and empirically, some of philosophy's most perennial metaphysical questions.

Neural electrode devices hold great promise to help people with the restoration of lost functions. However, research is lacking in the biomaterial design of a stable, long-term device. Glial scarring is initiated when a device is inserted into brain tissue and an inflammatory response ensues. Astrocytes become hypertrophic, hyperplastic, and upregulate glial-fibrillary acidic protein. This study was designed to investigate the astrocyte proliferation, viability, morphology, and gene expression to assess the reactive state of the cells on different material surfaces. Although platinum and silicon have been extensively characterized both in vivo and in vitro for their biocompatibility with neuronal cells, this study used the novel usage of PMMA and SU-8 in neural electrodes by comparative analysis of materials' biocompatibility. This study has shown evidence of noncytotoxicity of SU-8. We have also confirmed the biocompatibility of PMMA with astrocytes. Moreover, we have established sound guidelines of which neural implant materials should meet to be depicted biocompatible.

This article deals with the stability of poly-ethylenedioxythiopene (PEDOT) coatings under high loads of current pulses. Test parameters were chosen to match many peripheral nervous system applications in regard of charge injection, pulse width, and repetition frequency. PEDOT coatings were characterized with electrochemical impedance spectroscopes and pulse tests. After 60-100 million pulses, impedance increased and a more capacitive behavior was observed. A mean-time-to-failure of 127 million pulses could be calculated, suggesting a stable coating for at least this time frame with superior properties in regard of conventional platinum electrodes.

Neural implants are technical systems that restore sensory or motor functions after injury and modulate neural behavior in neuronal diseases. Neural interfaces or prostheses have lead to new therapeutic options and rehabilitation approaches in the last 40 years. The interface between the nervous tissue and the technical material is the place that determines success or failure of the neural implant. Recording of nerve signals and stimulation of nerve cells take place at this neuro-technical interface. Polymers are the most common material class for substrate and insulation materials in combination with metals for interconnection wires and electrode sites. This work focuses on the neuro-technical interface and summarizes its fundamental specifications first. The most common polymer materials are presented and described in detail. We conclude with an overview of the different applications and their specific designs with the accompanying manufacturing processes from precision mechanics, laser structuring and micromachining that are introduced in either the peripheral or central nervous system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010

The stability of the laser bonded titanium coated glass/polyimide microjoints were studied in vivo by implanting on a rat brain surface for 10 days. In the current state, the strength of the joints were measured by a specially designed instrument called "pressure test" equipment where the samples were subjected to a variable pressure load (using high pressure nitrogen) controlled by a pressure regulator. The strength of the joints seems to degrade by about 28% as a result of soaking in rat brain. The bond degradation in rat brain implants is similar compared with those soaked in artificial cerebrospinal fluid (CSF) solution. Polyimide uptakes water through existing pores in it and also water gets in the joint region through the edges of the samples. Water might have caused oxidation of the chemical bonds which are thought to have formed by the laser fabrication process. A separate set of samples were created using same parameters for testing the hermeticity of the laser bonds. The samples were also exposed to rat brain CSF and were tested for hermiticity at the end of 10 days exposure time. It was observed that the implanted samples retained their hermeticity although the bond strength degraded by about 28%.

The public interest in neural implants has grown considerably in recent years. Progress within related research areas in combination with increasing – albeit overly optimistic and indiscriminate – mass media coverage have led to the impression that the possibilities of neural prosthetics have grown enormously. But a closer look reveals that the reasons for the intensified interest are varied and cannot be attributed to technical progress alone. Some neural prostheses that have been under development for many years have not left the clinical development phase despite intensive research activities. Other implants, like cardiac pacemakers and cochlea implants, are mature products that have already been implanted in a large number of patients. From the public perspective and in media reports, progress in the development of neural implants is associated with new achievements in other fields of neuroscience. Communications on new applications of functional magnetic resonance imaging (fMRI) may suggest that a number of cognitive functions are now easily accessible with technological means. The fact that the interpretation of the results of fMRI studies depends on many conditions and is partly disputed also within the scientific community has been discussed in many publications but only very limited, in the general media. Besides this, research results and implementations in the area of electroencephalography and magnetoencephalography have sparked further debate on the question of free will, on determinism and indeterminism, and have attracted a large media response. The purpose of this paper is to discuss some societal and ethical aspects of neural implants from a technology assessment perspective. Technology assessment (TA) aims at providing knowledge about impacts and consequences of (new) technologies as well as about political and societal ways of dealing with them. It reflects about implementation conditions of technology and potential technology conflicts. Over the last years, neural implants became a subject for TA since they have gained a higher attention in both the political arena and the general public. Especially the ethical and social implications of technologies that electrically stimulate the brain and the possibilities of changing personality traits, changing moods, and perhaps enhancing human cognitive capabilities are central issues in related discussions. In this paper, we want to briefly summarize some of the key arguments as well as topics for future discussion and research.

in microelectrode technology. The clinical benefits of brain implants are far-reaching and include improvements in quality of life for patients suffering from neurological impairments and diseases, such as Parkinson’s disease, epilepsy, blindness, and paralysis. However, a number of major bottlenecks currently hinder the realization of the therapeutic potential of brain implants, one of which being the ability of the implant to function reliably over the remaining lifetime of the patient. It is generally believed that many complications in long-term implant functionality are due to an adverse brain tissue response elicited by the implant. This inflammatory response, featured by the formation of the astroglial scar, can result in isolation of the implant from target neurons both electrically and mechanically, and is arguably the biggest stumbling block in realizing chronic recordings from neural electrodes. A common strategy to dampen the tissue response is local delivery of anti-inflammatory drugs directly at the implant-tissue interface. [3–5] Although such approach has been shown to successfully moderate host response during the acute phase, [6] alone it may be inadequate to have long-term functional consequences, due to limitations in the duration of drug release. Since the sustained chronic tissue response to the implant is considered to be a result of both foreign body reaction [7] and mechanical mismatch induced micromotion, [8,9] we propose to modulate the sustained tissue response by endowing the implant with an intrinsic anti-inflammatory surface. Here, we demonstrate through both in vitro cell culture studies and in vivo rodent studies, that immobilized alpha-MSH creates an inherently anti-inflammatory neural electrode surface such that it significantly attenuates glial response for at least 4 weeks post-implantation. Alpha-MSH is an endogenous tridecapeptide that is secreted by pituitary cells, astrocytes, monocytes, keratinocytes, etc., and is found in the skin, brain, and other tissues. [10,11] Among its broad, potent anti-inflammatory functions, studies have shown alpha-MSH inhibits pro-inflammatory cytokines and neurotoxic nitric oxide (NO) production by microglia stimulated with beta-amyloid and interferon-gamma, which simulated inflammation associated with Alzheimer’s disease. [12] Since microglia, the resident macrophages in the brain, are the frontline defense cells against invasive implants, the neuroimmunomodulatory peptide alpha-MSH was selected in our study to directly mitigate microglial response to foreign brain implants. Coupling of the active molecule to the neural implant surface was accomplished through silane chemistry and the use of a hetero-bifunctional crosslinker with both thiol- and amino-reactive moieties, [13] as demonstrated in Figure 1. The surface coverage of alpha-MSH peptide was 0.0212 nmol cm –2 , quantified by application of sulfo-SDTB that reacts with primary amine, specifically in this case, those presented from the lysine residue and the N-terminus of the alpha-MSH peptide. In order to first investigate whether the alpha-MSH peptide remains biologically active when covalently immobilized to the Si surface, we cultured primary rat microglial cells on the peptide modified surface and subjected the culture to lipopolysaccharide (LPS) bacterial endotoxin, which elicits an inflammatory response in vitro. As shown in Figure 2A, the production of nitric oxide (NO), an indicator of inflammation, was reduced to nearly 50% of that observed in the control culture, suggesting that the anti-inflammatory property of alphaMSH was preserved during the tethering process. Moreover, we examined the gene expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) using real time RT-PCR. Both of these cytokines play a key role in mediating the inflammation process in vivo, and microglia are the known major cellular source for production of these cytokines. Modulating the level of TNFalpha and IL-1 is critical as excessive production of these factors could not only amplify the inflammation process by stimulating glial cell proliferation and activation, but also cause neuronal death. LPS is commonly used to induce microglial activation and cause production of neurotoxic pro-inflammatory cytokines. This is consistent with our finding where the mRNA expression level of TNF-alpha had an over three-fold increase in the control Si group after subjecting to LPS stimulation (Fig. 2B). In contrast, TNF-alpha expression

The major prerequisite for the clinical application of intracortical microelectrodes, or any other neural implant, is that the organism accepts them without causing an unacceptable degree of harm. However, all biomaterials, even those thought to be highly biocompatible, provoke a biological response and some degree of encapsulation. This means that the body can tolerate them, although they are not fully compatible. Therefore, a significant goal is to improve the knowledge and understanding of the interaction between the implanted devices and the local cellular environment in order to improve the long-term biotolerability, applicability, and functional perspectives of intracortical microelectrode arrays. In this article, some of the main challenges in this field that involves biomaterials science, bioengineering, neurology, neurosurgery, and neuroscience research are discussed.

Composite electrodes made of the polysaccharide agarose and carbon nanotube fibers (A-CNE) have shown potential to be applied as tissue-compatible, micro-electronic devices. In the present work, A-CNEs were functionalized using neuro-relevant proteins (laminin and alpha-melanocyte stimulating hormone) and implanted in brain tissue for 1 week (acute response) and 4 weeks (chronic response). Qualitative and quantitative analysis of neuronal and immunological responses revealed significant changes in immunological response to implanted materials depending on the type of biomolecule used. The potential to manipulate tissue response through the use of an anti-inflammatory protein, alpha-melanocyte stimulating hormone, was shown in the reduction of astroglia presence near the implant site during the glial scar formation. These results suggest that A-CNEs, which are soft, flexible, and easily made bioactive, have the ability to modify brain tissue response through surface modification as a function of the biomolecule used.

This optimization method for stereotaxic brain implants is based on seed/strand configurations of the basic type developed for the National Cancer Institute (NCI) atlas of regular brain implants. Irregular target volume shapes are determined from delineation in a stack of contrast enhanced computed tomography scans. The neurosurgeon may then select up to ten directions, or entry points, of surgical approach of which the program finds the optimal one under the criterion of smallest target volume diameter. Target volume cross sections are then reconstructed in 5-mm-spaced planes perpendicular to the implantation direction defined by the entry point and the target volume center. This information is used to define a closed line in an implant cross section along which peripheral seed strands are positioned and which has now an irregular shape. Optimization points are defined opposite peripheral seeds on the target volume surface to which the treatment dose rate is prescribed. Three different optimization algorithms are available: linear least-squares programming, quadratic programming with constraints, and a simplex method. The optimization routine is implemented into a commercial treatment planning system. It generates coordinate and source strength information of the optimized seed configurations for further dose rate distribution calculation with the treatment planning system, and also the coordinate settings for the stereotaxic Brown-Roberts-Wells (BRW) implantation device.

This paper specifically examines the implantation of a microelectrode array into the median nerve of the left arm of a healthy male volunteer. The objective was to establish a bi-directional link between the human nervous system and a computer, via a unique interface module. This is the first time that such a device has been used with a healthy human. The aim of the study was to assess the efficacy, compatibility, and long term operability of the neural implant in allowing the subject to perceive feedback stimulation and for neural activity to be detected and processed such that the subject could interact with remote technologies. A case study demonstrating real-time control of an instrumented prosthetic hand by means of the bi-directional link is given. The implantation did not result in infection, and scanning electron microscope images of the implant post extraction have not indicated significant rejection of the implant by the body. No perceivable loss of hand sensation or motion control was experienced by the subject while the implant was in place, and further testing of the subject following the removal of the implant has not indicated any measurable long term defects. The implant was extracted after 96 days. Copyright C 2004 John Wiley & Sons, Ltd.

Purpose: Use Monte Carlo simulations to determine the doseperturbation effects of a single column of radioactive seeds implanted in the brain.Material and Methods: The EGSnrc Monte Carlo simulation code together with an EGSnrc user code (BRACHYDOSnrc) was used to investigate doseperturbation effects in brain implant brachytheray using 125I. Doseperturbation effects resulting from the mutual attenuation or shielding of other seeds in the implant consisting between 8 and 12 seeds were investigated. The doseperturbation effects were calculated as the difference between the full Monte Carlo simulations taking into account the inhomogeneity caused by the presence of the seeds and the single seed superposition model which ignores the perturbation caused by other seeds in the implant. The seeds were arranged in a single column in a Perspex tubing (end‐to‐end) and calculation medium was water. Results: The results show that for 125I. seeds implanted into the brain, with no spacing between seeds, the single superposition dose calculation models underestimates the dose along the longitudinal direction of the seeds by up to 20%. The shielding effects of other seeds causes the doseperturbation which occur generally in the longitudinal direction of the seeds. The volume occupied by the difference in the dose distribution between the full Monte Carlo simulations and simple superposition model increases with increasing number of seeds as expected. The differences in the rest of the calculation grid was generally with ± 5%. Conclusions The differences between the full Monte Carlo simulations and the single seed superposition dose calculation is not clinically significant as differences occur close to the column of seeds where the dose is already high.

A biocompatible polymeric matrix system for the long-term controlled release of dopamine has been developed. Solid particles of this bioactive agent were encapsulated in ethylene-vinyl acetate copolymer (EVAc). Following immersion in an aqueous buffer solution, the release rate of dopamine from the polymer matrix was found to depend on the initial concentration of dopamine in the polymer. After coating the matrix devices with an additional impermeable layer of EVAc, constant rates of release were obtained by creating a cavity in this impermeable layer. The observed experiments are consistent with a diffusion-limited model of dopamine release; all the in vitro experimental results were therefore correlated by the effective diffusion coefficient of dopamine through the porous polymer network. These results are discussed in terms of potential design modifications to achieve desired release characteristics for a variety of neuroactive substances, including neurotransmitters or their precursors. o

We have previously shown that implanted fetal nerve tissue stimulates the regeneration of amputated chick limbs. The purpose of this study was to determine whether a similar phenomenon would occur in amputated rat limbs and if addition of applied direct current (DC) would affect this process. Thus, fetal nerve tissue was implanted into amputated stumps of 3-week-old rats; variable tissue regeneration was induced that was dependent on the age of the donor implant and the presence of applied DC. Twelve or 14 day fetal neural implants induced new accessory bones containing epiphyseal plates and marrow cavities and occasionally formed joint-like structures with the host humerus. Addition of DC to 12 day neural implants increased the number of new bones formed. Eighteen day neural tissue with applied DC did not induce new bone formation but stimulated the maximal elongation of the host humerus and outgrowth of nerve fibers to the cut surface. Implantation of fetal heart tissue or implantation of fetal neural tissue into unamputated limbs failed to induce new bone formation. Although true limb regeneration was not achieved, formation of new skeletal elements did occur and this effect was enhanced by applied DC.