External Pulse Generator Research Articles

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

Aims/hypothesisA new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents.MethodsRats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60% lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces were bilaterally implanted in the CSNs and attached to an external pulse generator. The rats were then randomised to KHFAC or sham modulation groups. KHFAC modulation variables were defined acutely by respiratory and cardiac responses to hypoxia (10% O2 + 90% N2). Insulin sensitivity was evaluated periodically through an ITT and glucose tolerance by an OGTT.ResultsKHFAC modulation of the CSN, applied over 9 weeks, restored insulin sensitivity (constant of the insulin tolerance test [KITT] HFHSu sham, 2.56 ± 0.41% glucose/min; KITT HFHSu KHFAC, 5.01 ± 0.52% glucose/min) and glucose tolerance (AUC HFHSu sham, 1278 ± 20.36 mmol/l × min; AUC HFHSu KHFAC, 1054.15 ± 62.64 mmol/l × min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin resistance and glucose intolerance returned to normal values within 5 weeks.Conclusions/interpretationKHFAC modulation of the CSN improves metabolic control in rat models of type 2 diabetes. These positive outcomes have significant translational potential as a novel therapeutic modality for the purpose of treating metabolic diseases in humans.

Peripheral Neurostimulation with a Microsize Wireless Stimulator.

Implementation of wireless technology enables tremendous reduction in the size of implantable neurostimulator devices. Without the need for tethering to an implantable pulse generator, a multitude of clinical applications can be envisioned, utilizing safe, rapidly implanted, economical, and culturally sensitive methods. External pulse generators providing power to implanted microsize wireless leads and/or contact pairs can be incorporated into belts, fabric, jewelry, and other suitable and convenient accoutrements. Microsized wireless neurostimulator lead placements can provide neuromodulation therapies without mechanically compromising normal physiological function in numerous anatomical locations not so accessible now. Avoiding implantation of the pulse generator dramatically reduces the expense of these therapies and can potentially lead to wider global access of care for neuromodulation in general.

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation

ObjectiveTo test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Patients and MethodsTen patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. ResultsWe observed blood oxygen level–dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. ConclusionThese findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. Trial Registrationclinicaltrials.gov Identifier: NCT01809613.

Compact high-power stable subnanosecond-pulsed YAG:Nd laser

A method is proposed for stable generation of powerful subnanosecond pulses without using reverse-feedback systems. This method requires no nonlinear elements inside the cavity and no external supplementary rf pulse generators in the shutter-control system. The method has been experimentally tested on a compact laser radiator based on a YAG:Nd crystal.

A pilot study of chronic pudendal nerve stimulation for faecal incontinence for those who have failed sacral nerve stimulation.

Sacral nerve stimulation (SNS) is used as a first-line treatment for faecal incontinence when conservative measures have failed. However, one-third of patients fail to benefit from this treatment. We hypothesised that sacral afferent stimulation can be maximised using pudendal nerve stimulation (PNS) and this may be of benefit in this patient group. The aim of this study was to assess chronic PNS for those who failed to improve with SNS. Ten patients who had failed SNS were recruited. All underwent percutaneous insertion of a stimulation lead with four-electrode array adjacent to the pudendal nerve. Continuous bipolar stimulation was administered using an external pulse generator over a 3-week period. Those who experienced a ≥50% reduction in the frequency of incontinent episodes over this period proceeded to chronic stimulation with an implantable pulse generator. Five patients experienced a ≥50% reduction of incontinent episodes during test stimulation and proceeded to chronic stimulation. In these five patients, at a median (range) follow-up of 24 (6-36) months, the median (inter quartile range) frequency of incontinent episodes reduced from 5 (18.25) to 2.5 (3) per week (p = 0.043). Three patients maintained a ≥50% improvement in soiling. There was an improvement in the St Mark's continence Score from 19 (15-24) to 16 (13-19), p = 0.042. There were no significant changes in ability to defer defecation or in quality of life scores. Pudendal nerve stimulation failed to improve the symptoms in the majority of patient who had failed SNS. Only a third experienced any improvement.

Surgical Paddle-Lead Placement for Screening Trials of Spinal Cord Stimulation

Spinal cord stimulation (SCS) has become an evidence-based treatment for a variety of chronic pain disorders. A key step in appropriate patient selection and long-term outcome predictability is a percutaneous screening trial of stimulation. Occasionally, a trial cannot be adequately completed with a percutaneous electrode. Rather than depriving this therapy from these patients, the authors have developed a program providing surgically implanted paddle-lead screening trials of SCS. Data from 22 patients undergoing paddle-lead screening trials of SCS from October 2009 to August 2012 were retrospectively reviewed. The surgical paddle leads were positioned with thoracic or cervical laminotomies under local anesthetic and conscious sedation, allowing awakened patients to confirm optimal lead placement. Externalized lead extensions were connected to an external pulse generator for a five-day screening trial. Pain reduction of at least 50% was required for patients to have the previously implanted paddle lead connected to an internalized pulse generator; otherwise, the trial surgical paddle leads were removed. Twenty-two patients received five-day paddle-lead stimulation screening trials for various chronic neuropathic pain conditions. All paddle screening trials were well tolerated and completed as outpatient procedures. Sixteen patients received fully implanted systems. At an average follow-up of 23 months, all implanted patients continue to have satisfactory pain control. There were no infections, lead migrations, or revisions. Surgically implanted paddle-lead screening trials of SCS can be used safely and effectively in those patients in which an adequate percutaneous-electrode trial cannot be completed. Results are similar to those seen with standard percutaneous screening trials. A systematic approach to surgical-paddle screening trials of SCS has not been previously reported.

Urgent‐SQ implant in treatment of overactive bladder syndrome: 9‐year follow‐up study

Electrical stimulation of the posterior tibial nerve (PTN) is an established therapy for the treatment of refractory overactive bladder syndrome (OAB). The Urgent-SQ™ is an implant that is surgically placed near the PTN and activated by an external pulse generator, allowing for "on demand" PTN stimulation, without the need for needle insertion. The current study presents results of a 9-year, open-label, follow-up of eight patients to address the long term safety and efficacy of the implant. In 2003, eight patients with refractory OAB received a Urgent-SQ™ implant and were systematically followed up for 1 year. After that, the follow up continued as open-label study. The seven patients who still had the implant were contacted after 9 years and evaluated with an interview, physical exam, ankle X-ray, voiding diaries, and completed questionnaires about adverse events, performance, efficacy, safety, and quality of life (validated iQoL). Six of the seven patients still had sensory and loco-motor responses on stimulation at 9-year follow-up. Three of four patients who had a successful treatment response at 1 year, still use the device. The fourth patient restarted therapy. The implants are intact with no migration and/or displacement. All patients reported easy handling of the Urgent-SQ™. One patient reported sporadic spontaneous sensory responses. One patient reported occasional localized ankle discomfort. After 9 years of clinical experience, we demonstrated that implant driven PTNS with the Urgent-SQ™ is a safe therapy for OAB. The implant has a long lifespan and is well tolerated by patients.

Preliminary evaluation of a silicon strip detector for photon-counting spectral CT

An edge-on silicon strip detector designed for photon-counting spectral computed tomography (CT) is presented. Progress on the development of an application specific integrated circuit (ASIC) to process the pulses and sort them into energy bins is reported upon. The ASIC and detector are evaluated in terms of electronic noise, energy resolution, count rate linearity under high-frequency periodic pulses, threshold variation and gain. The high-frequency periodic pulses are injected both by means of an external pulse generator and a pulsed laser illuminating the silicon diode. The pulsed laser system has ∼100ps pulse width and thus generates near instantaneous pulses in the diode, thus mimicking real X-ray conversions.The evaluation shows a low thermal noise level of 0.77keV RMS, an energy resolution of 1.5keV RMS when electron-hole pairs are generated in the detector diode by the laser injection. The test results furthermore indicate a good energy-discriminating capability of the detector with the thresholds spread out, assigning the external pulses to higher and higher energy bins as the pulse intensity is increased.

Short‐term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24-h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5-15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7-days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1-13.1) to 16.6 mmHg (95% CI 10.8-19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0-16.3) to 16.5 mmHg (95% CI 2.7-30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at 15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Short-term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.

Sacral nerve stimulation enhances epithelial barrier of the rectum: results from a porcine model

The mechanism of action of sacral nerve stimulation (SNS) remains largely elusive. The aims of this study were to develop a clinically relevant animal model for percutaneous SNS and to describe its effect on the epithelial barrier of the rectum. Under general anesthesia and after percutaneous electrode placement for S3 nerve root stimulation, six pigs underwent unilateral stimulation and six bilateral stimulation. Animals were stimulated for 3 h using an external pulse generator (1-2.5 V; 14 Hz; 210 μs). Six animals underwent electrode implantation without stimulation and served as controls. Full-thickness rectal biopsies were performed prior to and after stimulation. Paracellular permeability was evaluated by measuring sulfonic acid flux across the rectal mucosa in Ussing chambers. Histological assessment of mucosal thickness, epithelial desquamation, and mucus expression were performed. Percutaneous stimulation resulted in successful anal contractions whose amplitude and uniformity was enhanced following bilateral compared with unilateral stimulation. In controls, paracellular permeability significantly increased during the stimulation period whereas it remained unchanged following unilateral stimulation. In contrast, permeability was significantly reduced by bilateral stimulation. This effect was associated with a concomitant reduction in mucosal thickness and a trend toward increased amount of mucus on surface epithelium compared with controls. The development of a porcine model of percutaneous SNS revealed the ability of neuromodulation to reinforce rectal epithelial barrier. Furthermore, our results suggest that SNS could be used for treatment of gastrointestinal pathologies with reduced rectal mucosal barrier functions.

The Australian History of Cardiac Pacing: Memories from a Bygone Era

Although Dr Albert Hyman in New York is believed to have built the first cardiac pacemaker in 1932, he acknowledges Dr Mark Lidwell in Sydney, Australia as having not only built a pacemaker, but also successfully used it to resuscitate a newborn infant in or before 1929. Fully implantable pacemakers, however, were not possible until 1958, following the development of the silicon transistor. Within three years of that first implant, a pulse generator attached to epicardial leads was implanted at the Royal Melbourne Hospital. About the same time, an engineer in Sydney with intermittent complete heart block who had received epicardial leads and an external pulse generator proposed a simple sensing circuit, leading to the design of the first demand pacing system. By the mid 1960s, physicians were inserting transvenous leads in the right ventricle attached to pulse generators implanted in the anterior abdominal wall. In 1963, an Australian pacemaker company, Telectronics, was founded in Sydney. This innovative company-designed many of the features of transvenous leads and pulse generators we take for granted today. Australia also played a leading role in the design or early evaluation of the lithium power source, lead fixation, steroid elution, automatic anti-tachycardia pacing algorithms and the minute ventilation rate adaptive sensor. This manuscript describes the challenges and frustrations of those pioneers: physicians, surgeons and biomedical engineers.

Two‐channel gastric pacing in patients with diabetic gastroparesis

Our primary goals were to investigate the effects of two-channel gastric pacing on gastric myoelectrical activity, and energy consumption with the secondary intent to monitor gastric emptying and symptoms in patients with severe diabetic gastroparesis. Four pairs of temporary pacing wires were inserted on the serosa of the stomach at the time of laparotomy to place the Enterra™ System in 19 patients with severe gastroparesis not responding to standard medical therapies. Two of the pairs were for electrical stimulation and the other two for recording. Five days after surgery the optimal pacing parameters for the entrainment of gastric slow waves in each patient were identified by serosal recordings. Two-channel gastric pacing was then initiated for 6 weeks using a newly developed external multi-channel pulse generator. Electrogastrogram (EGG), Total Symptom Score (TSS), and a 4-h gastric emptying test were assessed at baseline and after 6 weeks of active gastric pacing. Enterra™ device was turned OFF during the duration of this study. Two-channel gastric pacing at 1.1 times the intrinsic frequency entrained gastric slow waves and normalized gastric dysrhythmia. After 6 weeks of gastric pacing, tachygastria was decreased from 15 ± 3 to 5 ± 1% in the fasting state and from 10 ± 2 to 5 ± 1% postprandially (P < 0.05), mean TSS was reduced from 21.3 ± 1.1 to 7.0 ± 1.5 (P < 0.05) and mean 4-h gastric retention improved from 42 to 28% (P = 0.05). Two-channel gastric pacing is a novel treatment approach which is able to normalize and enhance gastric slow wave activity as well as accelerate gastric emptying in patients with diabetic gastroparesis with a goal safety profile.

A 3D Electroactive Polypyrrole-Collagen Fibrous Scaffold for Tissue Engineering

Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal or muscular cells. Here we report on the fabrication of polypyrrole-incorporated collagen-based fibers via interfacial polyelectrolyte complexation (IPC). The mean ultimate tensile strength of the fibers is 304.0 ± 61.0 MPa and the Young’s Modulus is 10.4 ± 4.3 GPa. Human bone marrow-derived mesenchymal stem cells (hMSCs) are cultured on the fibers in a proliferating medium and stimulated with an external electrical pulse generator for 5 and 10 days. The effects of polypyrrole in the fiber system can be observed, with hMSCs adopting a neuronal-like morphology at day 10, and through the upregulation of neural markers, such as noggin, MAP2, neurofilament, β tubulin III and nestin. This study demonstrates the potential of this fiber system as an attractive 3D scaffold for tissue engineering, where collagen is present on the fiber surface for cellular adhesion, and polypyrrole is encapsulated within the fiber for enhanced electrical communication in cell-substrate and cell-cell interactions.

Electrical and dielectric characteristics of Al/polyindole Schottky barrier diodes. II. Frequency dependence

AbstractThe dielectric properties and ac electrical conductivity of Al/polyindole (Al/PIN) Schottky barrier diodes (SBDs) were investigated by using admittance spectroscopy (capacitance–voltage [C‐V] and conductance–voltage [G/ω‐V]) method. These C‐V and G/ω‐V characterizations were performed in the frequency range of 1 kHz to 10 MHz by applying a small ac signal of 40 mV amplitude from the external pulse generator, whereas the dc bias voltage was swept from (−10 V) to (+10 V) at room temperature. The values of dielectric constant (ε′), dielectric loss (ε″), dielectric loss tangent (tanδ), real and imaginary part of electrical modulus (M′ and M″), ac electrical conductivity (σac), and series resistance (Rs) of the Al/PIN SBDs were found to be quite sensitive to frequency and applied bias voltage at relatively low frequencies. Although the values of the ε′, ε″, tanδ, and Rs of the device were observed to decrease with increasing frequencies, the electric modulus and σac increased with increasing frequency for the high forward bias voltages. These results revealed that the interfacial polarization can more easily occur at low frequencies and that the majority of interface states (Nss) between Al and PIN, consequently, contribute to deviation of dielectric properties of the Al/PIN SBDs. Furthermore, the voltage‐dependent profile of both Rs and Nss were obtained from the C‐V and G/ω‐V characteristics of the Al/PIN SBDs at room temperature. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

TID Effects in Deep N-Well CMOS Monolithic Active Pixel Sensors

This paper is devoted to the study of total ionizing dose effects in deep N-well (DNW) CMOS monolithic active pixel sensors (MAPS) for particle tracking fabricated in a STMicroelectronics 130 nm process. DNW-MAPS samples were exposed to gamma-rays up to a final dose of 1100 krad(SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) and then subjected to a 100degC annealing cycle. Ionizing radiation tolerance was tested by monitoring the device noise properties and its response to charge injection through an external pulse generator throughout the irradiation and annealing campaign. The origins of performance degradation are discussed based on the results from radiation hardness characterization of single transistors belonging to the same CMOS technology and of test diodes reproducing the MAPS collecting electrode structure. Also circuit simulations have been performed to supply further evidence for the proposed degradation mechanisms.

Evaluation of changes in cardiac biomarker concentrations and enzyme activities in serum after short- and long-duration transcutaneous cardiac pacing in dogs

To evaluate serum cardiac biomarker concentrations and selected enzyme activities in dogs with experimentally induced bradyarrhythmias after short- (1-hour) and long- (3-hour) duration transcutaneous cardiac pacing (TCP). 10 healthy Beagles. In each dog, anesthesia was induced with propofol (5 mg/kg, IV) and maintained via inhalation of isoflurane in oxygen. To induce bradyarrhythmia, diltiazem was administered IV (20 to 50 mg/dog). Transcutaneous cardiac pacing was performed for 1 hour (5 dogs) or 3 hours (5 dogs) by use of an automated external cardiac pulse generator and a transdermal electrode. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase were evaluated the day before (baseline) and at intervals until 7 days after TCP. Increases (from baseline) in serum cardiac biomarker concentrations and enzyme activities were detected in the long-duration TCP group; changes in the short-duration TCP group were more minor and largely not significant. Although severity of myocardial and skeletal muscular injuries was apparently greater with greater duration of TCP, the injuries were not persistent; most variables were within reference range within 3 days after TCP. Results indicated that application of TCP for > 1 hour in dogs may cause myocardial and skeletal muscular injuries. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase should be more carefully monitored after TCP of > 1 hour's duration to evaluate potential myocardial damages.

Use of tunnelled active fixation leads allows reliable temporary pacing over prolonged periods

Temporary tunnelled pacing (TTP) is an alternative method of providing temporary pacing in which an active fixation permanent pacing lead is placed fluoroscopically through percutaneous venous access, tunnelled subcutaneously and connected to a resterilized external pulse generator. Our study shows that temporary tunnelled pacing is a safe and reliable method of achieving prolonged temporary pacing. We believe that temporary tunnelled pacing should be considered as an option in all patients who have an indication for prolonged temporary pacing.

DEEP BRAIN STIMULATION FOR OBSESSIVE-COMPULSIVE DISORDER

To demonstrate the pattern of activation associated with electrical stimulation through bilateral deep brain stimulation electrodes placed within the anterior limb of the internal capsule to the level of the ventral striatum for treatment of obsessive-compulsive disorder. A 44-year-old man with a 26-year history of obsessive-compulsive disorder underwent functional magnetic resonance imaging (fMRI) and deep brain stimulation-evoked cortical potential testing after bilateral implantation of deep brain stimulation leads. Stimulation was delivered independently through the distal two contacts of each percutaneously extended lead using an external pulse generator. On postoperative Day 2, we used a 3-Tesla magnetic resonance system to measure changes in the fMRI blood oxygen level-dependent signal using stimulation parameters that were predetermined to demonstrate behavioral effects. All studies were well tolerated. Trial stimulations performed intraoperatively as well as on postsurgical Day 1 were associated with acutely elevated mood and reduced anxiety. Although the benefit achieved acutely was relatively symmetric between the bilaterally placed leads, follow-up programming showed a clear advantage to right-sided stimulation. Three of the four fMRI trials demonstrated good activation, with the fourth being moderately corrupted by motion artifact. The beneficial effects observed with right-sided stimulation were associated with activation of the ipsilateral head of the caudate, medial thalamus, and anterior cingulate cortex as well as the contralateral cerebellum. The distribution of the cortical evoked potentials was consistent with the locus of cortical activation observed with fMRI. High-frequency stimulation via a lead placed in the anterior limb of the internal capsule induced widespread hemodynamic changes at both the cortical and subcortical levels including areas typically associated with the pathogenesis of obsessive-compulsive disorder.

Parkinson Disease: Pattern of Functional MR Imaging Activation during Deep Brain Stimulation of Subthalamic Nucleus—Initial Experience

To prospectively determine the pattern of functional magnetic resonance (MR) imaging activation at 3 T produced by deep brain stimulation (DBS) of subthalamic nucleus (STN) for treatment of Parkinson disease and to determine the safety of DBS electrode stimulation during functional MR imaging at 3 T. Informed consent was obtained from all subjects participating in the study, and the study protocol was approved by the institutional review board at the Cleveland Clinic Foundation and was HIPAA compliant. After extensive phantom safety testing of DBS lead systems, five patients (three men, two women; mean age, 49.4 years +/- 14.5 [standard deviation]; range, 31-74 years) with percutaneously extended bilateral DBS electrodes placed in the STN for treatment of Parkinson disease were examined at 3 T on the 1st or 2nd postoperative day. Imaging consisted of a three-dimensional anatomic data set with leads disconnected and a blood oxygen level-dependent functional MR image with a single lead connected to the external pulse generator in the MR imaging control room by using stimulation parameters previously determined to produce optimal stimulation for alleviation of symptoms. A total of nine leads were tested with the functional MR imaging protocol. Subjects underwent neurologic examination immediately before and after MR imaging. All five patients completed the study without change in their neurologic examination and with activation seen in eight of nine electrodes stimulated. Activation was seen in the ipsilateral basal ganglia in all subjects and ipsilateral thalamus in six of the electrodes tested. Two of the electrode stimulations demonstrated additional activation in the STN and/or substantia nigra region adjacent to the electrode tip. For three electrode stimulations, activation was seen in the contralateral superior cerebellum. Therapeutically effective DBS of STN can be performed safely during functional MR imaging at 3 T and produces a consistent pattern of ipsilateral activation of deep brain motor structures.

A Preliminary Feasibility Study of Different Implantable Pulse Generators Technologies for Diaphragm Pacing System

Diaphragm pacing stimulation (DPS) for ventilator-dependent patients provides several advantages over conventional techniques such as phrenic nerve pacing or mechanical ventilator support. To date, the only existing system for DPS uses lead electrodes, percutaneously attached to an external pulse generator (PG). However, for a widespread use of this technique it would be more appropriate to eliminate the need for percutaneous wire and use a totally implantable system. The aim of this study was to determine if it were feasible to replace the external PG by an implantable system. We present here the results of a preliminary study of two different PG, currently used in other electrical stimulation (ES) clinical applications, which could be used as implantable DPS systems. One radio-frequency-powered PG, one rechargeable battery-powered PG, and the current external PG were tested. Each was attached to the externalized part of the wires, connected to the diaphragm and tidal volume (TV) was measured in one ventilator-dependent patient who has been using the current percutaneous stimulator for 3 years. Results indicated that both implantable PGs could achieve equivalent ventilatory requirements to the current external stimulator. No significant differences were observed between the three PG systems when stimulating the electrodes as used in the patient's own chronically attached PG system. We found that TV increased with increases in charge and frequency as expected when stimulating the patient's electrodes individually and in combination with each PG system. These results are a significant step toward developing a totally implantable DPS system for the ventilator-dependant patients. Further clinical tests to demonstrate the safety and efficacy of a fully implanted DPS system are warranted.