A CMOS/SOI single-input PWM discriminator for low-voltage body-implanted applications

A CMOS/SOI circuit to decode Pulse-Width Modulation (PWM) signals is presented as part of a body-implanted neurostimulator for visual prosthesis. Since encoded data is the sole input to the circuit, the decoding technique is based on a novel double-integration concept and does not require low-pass filtering. Non-overlapping control phases are internally derived from the incoming pulses and a fast-settling comparator ensures good discrimination accuracy in the megahertz range. The circuit was integrated on a 2 mum single-metal thin-film CMOS/SOI fabrication process and has an effective area of 2 mm(2). Measured resolution of encoding parameter a is better than 10% at 6 MHz and V-DD = 3.3 V. Idle-mode consumption is 340 LW. Pulses of frequencies up to 15 MHz and alpha = 10% can be discriminated for 2.3 V less than or equal to V-DD less than or equal to 3.3 V. Such an excellent immunity to V-DD deviations meets a design specification with respect to inherent coupling losses on transmitting data and power by means of a transcutaneous link.

A low-power silicon-on-insulator PWM discriminator for biomedical applications

A CMOS/SOI circuit to decode PWM signals is presented as part of a body-implanted neurostimulator for visual prosthesis. Since encoded data is the sole input to the circuit, the decoding technique is based on a double-integration concept and does not require dc filtering. Nonoverlapping control phases are internally derived from the incoming pulses and a fast-settling comparator ensures good discrimination accuracy in the megahertz range. The circuit was integrated on a 2 mu m single-metal SOI fabrication process and has an effective area of 2mm(2) Typically, the measured resolution of encoding parameter a was better than 10% at 6MHz and V-DD=3.3V. Stand-by consumption is around 340 mu W. Pulses with frequencies up to 15MHz and alpha = 10% can be discriminated for V-DD spanning from 2.3V to 3.3V. Such an excellent immunity to V-DD deviations meets a design specification with respect to inherent coupling losses on transmitting data and power by means of a transcutaneous link.

Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors

The development of drugs for the control of tumor angiogenesis requires a simple, accurate, and economical assay for tumor-induced vascularization. We have adapted the orthotopic implantation model to angiogenesis measurement by using human tumors labeled with Aequorea victoria green fluorescent protein for grafting into nude mice. The nonluminous induced capillaries are clearly visible against the very bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. The orthotopic implantation model of human cancer has been well characterized, and fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. Intravital images of orthotopically implanted human pancreatic tumors clearly show angiogenic capillaries at both primary and metastatic sites. A quantitative time course of angiogenesis was determined for an orthotopically growing human prostate tumor periodically imaged intravitally in a single nude mouse over a 19-day period. Whole-body optical imaging of tumor angiogenesis was demonstrated by injecting fluorescent Lewis lung carcinoma cells into the s.c. site of the footpad of nude mice. The footpad is relatively transparent, with comparatively few resident blood vessels, allowing quantitative imaging of tumor angiogenesis in the intact animal. Capillary density increased linearly over a 10-day period as determined by whole-body imaging. Similarly, the green fluorescent protein-expressing human breast tumor MDA-MB-435 was orthotopically transplanted to the mouse fat pad, where whole-body optical imaging showed that blood vessel density increased linearly over a 20-week period. These powerful and clinically relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological microenvironments.

Understanding data flow and security requirements in wireless Body Area Networks for healthcare

The Body Area Network (BAN) is an emerging technology that focuses on monitoring physiological data in, on and around the human body. BAN technology permits wearable and implanted sensors to collect vital data about the human body and transmit it to other nodes via low-energy communication. In this paper, we investigate interactions in terms of data flows between parties involved in BANs under four different scenarios targeting outdoor and indoor medical environments: hospital, home, emergency and open areas. Based on these scenarios, we identify data flow requirements between BAN elements such as sensors and control units (CUs) and parties involved in BANs such as the patient, doctors, nurses and relatives. Identified requirements are used to generate BAN data flow models. Petri Nets (PNs) are used as the formal modelling language. We check the validity of the models and compare them with the existing related work. Finally, using the models, we identify communication and security requirements based on the most common active and passive attack scenarios.

The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants.

Although the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).

Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. Drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

Radiowave propagation from a tissue-implanted source at 418 MHz and 916.5 MHz

Tissue-implanted ultra-high frequency (UHF) radio devices are being employed in both humans and animals for telemetry and telecommand applications, This paper describes the experimental measurement and electromagnetic modeling of propagation from 418-MHz and 916.5-MHz sources placed in the human vagina. Whole-body homogeneous and semi-segmented software models were constructed using data from the Visible Human Project. Bodyworn radiation efficiencies for a vaginally placed 418-MHz source were calculated using finite-difference time-domain and ranged between 1.6% and 3.4% (corresponding to net body losses of between 14.7 and 18.0 dB), Greater losses were encountered at 916.5 MHz, with efficiencies between 0.36% and 0.46% (net body loss ranging between 23.4 and 24.4 dB), Practical measurements were in good agreement with simulations, to within 2 dB at 418 MHz and 3 dB at 916.5 MHz. The degree of tissue-segmentation for whole-body models was found to have a minimal effect on calculated azimuthal radiation patterns and bodyworn radiation efficiency, provided the region surrounding the implanted source was sufficiently detailed.

Robust implantable antenna for in-body communications

A compact implantable printed meandered folded dipole antenna with a volume of 101.8 mm3 and robust performance is presented for operation in the 2.4 GHz medical ISM bands. The implant antenna is shown to maintain its return loss performance in the 2360???2400 MHz, 2400???2483.5 MHz and 2483.5???2500 MHz frequency bands, simulated in eleven different body tissue types with a broad range of electrical properties. Bandwidth and resonant frequency changes are reported for the same antenna implanted in high water content tissues such as muscle and skin as well as low water content tissues such as subcutaneous fat and bone. The antenna was also shown to maintain its return loss performance as it was moved towards a tissue boundary within a simulated phantom testbed.

Energy-efficient hybrid system for Wireless Body Area Network Applications

Wireless Body Area Networks (WBANs) consist of a number of miniaturized wearable or implanted sensor nodes that are employed to monitor vital parameters of a patient over long duration of time. These sensors capture physiological data and wirelessly transfer the collected data to a local base station in order to be further processed. Almost all of these body sensors are expected to have low data-rate and to run on a battery. Since recharging or replacing the battery is not a simple task specifically in the case of implanted devices such as pacemakers, extending the lifetime of sensor nodes in WBANs is one of the greatest challenges. To achieve this goal, WBAN systems employ low-power communication transceivers and low duty cycle Medium Access Control (MAC) protocols. Although, currently used MAC protocols are able to reduce the energy consumption of devices for transmission and reception, yet they are still unable to offer an ultimate energy self-sustaining solution for low-power MAC protocols. This paper proposes to utilize energy harvesting technologies in low-power MAC protocols. This novel approach can further reduce energy consumption of devices in WBAN systems.

A survey on wireless body area networks for eHealthcare systems in residential environments

The progress in wearable and implanted health monitoring technologies has strong potential to alter the future of healthcare services by enabling ubiquitous monitoring of patients. A typical health monitoring system consists of a network of wearable or implanted sensors that constantly monitor physiological parameters. Collected data are relayed using existing wireless communication protocols to the base station for additional processing. This article provides researchers with information to compare the existing low-power communication technologies that can potentially support the rapid development and deployment of WBAN systems, and mainly focuses on remote monitoring of elderly or chronically ill patients in residential environments.

Functional relationship between subfrnical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel carmula were implanted into their SFO. The volume of injection was 0.2 mu l. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 mu g), L-NAME (40 mu g) and LAR (30 mu g) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 mu g) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis. (c) 2007 Elsevier B.V All rights reserved.

Compensatory rebound of body movements during sleep, after asphyxia in neonatal rats

OBJETIVO: A utilidade dos movimentos corporais (MC) que ocorrem durante o sono para diagnosticar e predizer as conseqüências, em longo prazo, da asfixia perinatal é contraditório. Este estudo investigou se ratos recém-nascidos (RN) manifestam MC em resposta compensatória à asfixia, e se estas alterações podem ter alguma importância na sua patogênese. MÉTODOS: Oito ratos RN (6-48h de vida) foram submetidos à implantação de pequenos eletrodos para registros da eletromiografia e eletrocardiografia. Os MC e a freqüência cardíaca (FC) foram registrados durante períodos de 30 min: fase controle (F1), fases de asfixia (F2; F3) e fase de recuperação pós-asfixia (F4). A asfixia foi promovida pelo envolvimento completo do animal com uma lâmina de polivinil. RESULTADOS: A FC diminuiu progressivamente durante F2 e F3 até a bradicardia. em F2 houve grande agitação dos animais e aumento dos períodos de vigília. em F3 houve redução significante dos MC de 12,5 ± 0,5 (Md ± SE/2min) para 9,0 ± 0,44 (P<0,05). A freqüência dos MC aumentou em F4 para 15,0 ± 0,49. CONCLUSÃO: Estes dados mostram que ratos RN com asfixia apresentam MC compensatórios durante o sono que podem ajudar no diagnóstico desta afecção e de outros problemas relacionados aos parâmetros do sono.

Dynamics of the interaction between body fluid and Ti cp: the influence of surface functionalization in the first stages of osseointegration

INTRODUCTION: Regenerative therapies using biomaterials require accurate information on interactions between the implanted material and the human body. To improve the process of bone regeneration it is necessary to obtain a better understanding of the influence of the surfaces on the early stages of osseointegration. This work aims to investigate the dynamic interaction between simulated body fluid (SBF) and titanium surfaces (Ti cp) immediately after their first contact. METHODS: Ti cp samples were passed through physicochemical treatments after immersion in acid solution, alkaline solution and solutions containing TiO2 and Ca2+, to obtain three different surfaces. These were characterized by electron microscopy and free energy estimates. The evaluation of the interaction with SBF was performed by measuring the dynamic contact angles after contacting the surfaces. RESULTS: The effects of SBF wettability were more significant on surfaces according to high energy estimates. A comparative analysis of the three types of surfaces showed that fluid spreading was greater in samples with greater polar components, indicating that the surface nature influences interactions in the early stages of osseointegration. CONCLUSION: The results indicate the influence of polar interactions in the dynamic wettability of the SBF. It is possible that these interactions can also influence cellular viability on surfaces. Based on these results, new experiments are being designed to improve the presented methodology as a tool for the evaluation of biomaterials without the need for in vivo experiments.

Metabolic Improvements in Obese Type 2 Diabetes Subjects Implanted for 1 Year with an Endoscopically Deployed Duodenal-Jejunal Bypass Liner

Background: The purpose of this study was to evaluate the effect of the duodenal-jejunal bypass liner (DJBL), a 60-cm, impermeable fluoropolymer liner anchored in the duodenum to create a duodenal-jejunal bypass, on metabolic parameters in obese subjects with type 2 diabetes. Methods: Twenty-two subjects (mean age, 46.2 +/- 10.5 years) with type 2 diabetes and a body mass index between 40 and 60 kg/m(2) (mean body mass index, 44.8 +/- 7.4 kg/m(2)) were enrolled in this 52-week, prospective, open-label clinical trial. Endoscopic device implantation was performed with the patient under general anesthesia, and the subjects were examined periodically during the next 52 weeks. Primary end points included changes in fasting blood glucose and insulin levels and changes in hemoglobin A1c (HbA1c). The DJBL was removed endoscopically at the end of the study. Results: Thirteen subjects completed the 52-week study, and the mean duration of the implant period for all subjects was 41.9 +/- 3.2 weeks. Reasons for early removal of the device included device migration (n = 3), gastrointestinal bleeding (n = 1), abdominal pain (n = 2), principal investigator request (n = 2), and discovery of an unrelated malignancy (n = 1). Using last observation carried forward, statistically significant reductions in fasting blood glucose (-30.3 +/- 10.2 mg/dL), fasting insulin (-7.3 +/- 2.6 mu U/mL), and HbA1c (-2.1 +/- 0.3%) were observed. At the end of the study, 16 of the 22 subjects had an HbA1c < 7% compared with only one of 22 at baseline. Upper abdominal pain (n = 11), back pain (n = 5), nausea (n = 7), and vomiting (n = 7) were the most common device-related adverse events. Conclusions: The DJBL improves glycemic status in obese subjects with diabetes and therefore represents a nonsurgical, reversible alternative to bariatric surgery.

Vertebral body stenting: a new method for vertebral augmentation versus kyphoplasty

Vertebroplasty and kyphoplasty are well-established minimally invasive treatment options for compression fractures of osteoporotic vertebral bodies. Possible procedural disadvantages, however, include incomplete fracture reduction or a significant loss of reduction after balloon tamp deflation, prior to cement injection. A new procedure called "vertebral body stenting" (VBS) was tested in vitro and compared to kyphoplasty. VBS uses a specially designed catheter-mounted stent which can be implanted and expanded inside the vertebral body. As much as 24 fresh frozen human cadaveric vertebral bodies (T11-L5) were utilized. After creating typical compression fractures, the vertebral bodies were reduced by kyphoplasty (n = 12) or by VBS (n = 12) and then stabilized with PMMA bone cement. Each step of the procedure was performed under fluoroscopic control and analysed quantitatively. Finally, static and dynamic biomechanical tests were performed. A complete initial reduction of the fractured vertebral body height was achieved by both systems. There was a significant loss of reduction after balloon deflation in kyphoplasty compared to VBS, and a significant total height gain by VBS (mean +/- SD in %, p < 0.05, demonstrated by: anterior height loss after deflation in relation to preoperative height [kyphoplasty: 11.7 +/- 6.2; VBS: 3.7 +/- 3.8], and total anterior height gain [kyphoplasty: 8.0 +/- 9.4; VBS: 13.3 +/- 7.6]). Biomechanical tests showed no significant stiffness and failure load differences between systems. VBS is an innovative technique which allows for the possibly complete reduction of vertebral compression fractures and helps maintain the restored height by means of a stent. The height loss after balloon deflation is significantly decreased by using VBS compared to kyphoplasty, thus offering a new promising option for vertebral augmentation.