Introduction
A neuromodulation system may consist of two or more components, including the neurostimulator, a lead which contains the electrodes for stimulation and, in some cases, an extension that bridges the connection between the neurostimulator and the lead. It is important to understand both the therapies as well as the technology and engineering trade-offs when designing implantable neuromodulation systems (INS). This chapter will focus on device physical design and materials, as well as device safety considerations, with specific focus on deep brain stimulation (DBS) and spinal cord stimulation (SCS) systems.
Neurostimulator form factor and materials
Device construction
An implantable neurostimulation system, or INS, consists of six main components: the device enclosure, a power source, electronics circuitry, communication and/or recharge antenna, feedthroughs, and the device connector/header ( Figure 9.1 ). These systems may be classified into three types based on their power source: rechargeable, primary power source, and transcutaneous inductively-coupled devices. Most of the systems implanted today for DBS and SCS are rechargeable or primary power source devices.
The device enclosure is a hermetic package. The power source and electronics circuitry are contained within this hermetic device enclosure to ensure safe containment and prevention of body fluids from contacting these components and, conversely, to prevent potentially harmful substances present in the internal components from reaching the body. In rechargeable devices, typically a magnetic or radiofrequency (RF) energy is transferred from an external instrument with a transmitting antenna to a receiving antenna located on or inside the INS.
Communication to the electronics circuitry is done with wireless telemetry to an antenna located within the electronics circuitry. An external instrument, such as a patient programmer or a clinician programmer, may be used to establish communication with the device in order to obtain device status updates or adjust stimulation parameters. A clinician programmer may provide a greater range of adjustment than a patient programmer, as the patient may be restricted to certain ranges of use by the clinician, depending on the specific therapy and system.
The device header houses the electrical contacts that mate with the proximal extension or lead connectors. The number of these contacts matches the number of independently programmable electrodes on the distal end of the lead. The extension or lead is inserted, positioned, and secured inside the device header. Each electrical contact in the device header connects to a feedthrough conductor. The feedthroughs are electrical conductors that carry the stimulation current from the electronics circuitry through the hermetic enclosure. These feedthroughs are made of an insulative material, such as glass or ceramic, to maintain the electrical isolation between each other and from the device conductive enclosure material. The material of the device header electrically insulates the connection of each feedthrough conductor. The header configuration determines how many different leads can be utilized by the device. The header typically mates with single lead or dual lead systems with four to eight electrodes per lead.
Implant locations and form factor
The physical form factor of the INS is derived by balancing the clinical therapy needs with the technology and engineering attributes of the device. These attributes include: number of leads and electrodes, power source type and capacity, and the stimulation output capabilities of the electronics.
Significant technological advances in power sources, electronics circuitry, and connector interconnects have allowed reductions in the size of the INS. The sizes of implantable neurostimulation devices, as measured by total volume, range from very small at 0.2 mL to relatively large at 50 mL. The size of the INS can restrict where the device is implanted, with the larger devices (greater than 20 mL) typically implanted in a subcutaneous or submuscular pocket located below the subclavicular region, lower abdomen or upper buttocks ( Figure 9.2 ).
The size of the implanted device is primarily driven by the number of therapy electrodes that may be activated for stimulation and the type and capacity of the power source. In general, rechargeable devices or transcutaneous inductively coupled devices are smaller. Neuromodulation therapies that require less stimulation energy or use a lower number of electrical contacts are significantly smaller in size. These smaller devices are implanted in different areas of the body and typically are implanted closer to the target therapy site. For example, the cochlear transcutaneous inductively coupled powered implants are small enough for implantation in the mastoid process in the skull. Implanting the device closer to the target therapy site also has advantages in minimizing lead migration and conductor fracture failures.
The device shapes and form factors are also designed to minimize tissue and skin erosion using rounded edges and large edge radii. The form factor and especially the thickness are key considerations for implant location. Lower abdomen implant locations can tolerate thicker and larger devices; for example, cardiac defibrillators with a volume greater than 200 mL and a thickness of 20 mm have been implanted in this region. In contrast, the subclavicular region requires thinner and smaller devices to prevent skin erosion. Smaller devices also provide an improved cosmesis effect for the patient to better conceal the system within subcutaneous tissues. Device form factors for SCS and DBS are shown in Figure 9.3 .
All devices, extensions, leads, and accessories are supplied packaged and sterilized. However, infection at the incision sites is a potential complication for patients who receive implanted neurostimulation systems. In one study, they found that most infections with implanted DBS devices were associated with the pocket location and that the infection agents were those most commonly associated with skin-based infections . With infections that involve the areas of the INS or extension, partial hardware removal sparing the lead accompanied by a course of postoperative intravenously administered antibiotics was successful in treating the infection in most cases . Similarly, infections involving the incision site of SCS systems also tend to involve the pocket location . The use of perioperative prophylactic antibiotics has been suggested for infection control .
Implant considerations for recharge and telemetry
Implanting depth is an important consideration for recharge and telemetry. Implanting the device too shallow can result in skin erosion, while implanting the device too deep can result in poor telemetry communication and recharge coupling. The recharge power transmission is significantly reduced with deeper implant depths. Implant depths of less than 1.5–2 cm are often recommended for rechargeable systems. The receiving recharge antenna is sometimes located toward or external to one side of the implanted device. Keeping the recommended recharge receiving antenna orientation is important for consistent recharge coupling performance. These devices are often sutured in place to prevent device flipping or migration.
Device materials and biocompatibility
Materials that are implanted in the human body are biocompatible and biostable for the designed application. Device manufacturers ensure that materials implanted in the body meet all required standards for implantable medical devices. International standards for biological evaluations of medical device materials include ISO 10993-1 which outline a set of comprehensive tests and protocols required for medical devices. The materials are categorized based on the type of body contact that the medical device has with the human body. The standard outlines four types of body contact: non-contacting medical devices, surface-contacting devices, external communicating devices, and implanted devices.
Implanted medical devices are further defined based on the specific application sites of the device. These sites are categorized into two different groups: direct tissue/bone or blood contact. In addition to the site of the implant, the required tests also vary depending on the duration of the implant or contact. The IS0 10993-1 standard categorizes three different periods of exposure: limited exposure, prolonged exposure or permanent exposure. Implanted neurostimulation devices have been evaluated by these biological tests including cytotoxicity, sensitization, irritation or intracutaneous reactivity, systemic toxicity, subacute and subchronic toxicity, genotoxicity, and hemocompatibility to ensure biocompatibility. In addition to biocompatibility, the biostability of the materials and designs that are implanted are evaluated. This biostability evaluation includes detailed mechanical, electrical, and chemical characterization of the material properties after being subjected to the human body for the defined exposure. Materials that are resistant to degradation and corrosion are key characteristics that the device manufacturers consider when selecting materials for chronic, implantable systems such as neurostimulation devices.
The materials of the implanted device that have direct tissue contact for permanent exposure periods include the device enclosure, device header and, with some designs, the recharge receiving antenna. Titanium is the most common material used for the hermetic package. It exhibits high levels of corrosion resistance, is non-magnetic, lightweight, non-toxic and biologically compatible with human tissue and bone. Titanium also has excellent mechanical strength and durability characteristics. It is often formed into thin-walled shield halves that are laser welded together to create the hermetic enclosure. For device systems that implement monopolar stimulation, this titanium hermetic package is utilized as the return common electrode. Titanium has several implantable grades. Commercially pure titanium, such as Grade 1 or 2, is most commonly used. Commercially pure titanium has excellent formability and elongation which allows cold working and forming of custom device shapes and a relatively tight bend radius. Other titanium alloys, such as Grade 9 or 23, include other alloys such as aluminum or vanadium which increase the electrical resistivity of the material. This increase in electrical resistivity results in lower magnetic eddy current loss during inductive power transfer used with rechargeable systems. These alloys do not have the formability or elongation properties of commercially pure titanium which translates into larger bend radius constraints for the device form factor. However, the improved recharge performance allows the device to be implanted deeper.
The receiving recharge coil is sometimes located external to the hermetic titanium package. This also improves the efficiency of the power transmission. When the receiving coil is located external to the hermetic titanium enclosure, it is packaged in magnetically transparent materials such as polyurethane, silicone rubber, polysulfone, ceramic, glass or biocompatible epoxy.
The electrical contacts in the device header are typically made from titanium, platinum, or iridium alloy materials. Commonly used insulating materials include polyurethane, silicone rubber, polysulfone, and biocompatible epoxy.
Lead system configuration and materials
The portion of the neurostimulation system that connects proximally to the neurostimulator and contains the electrodes distally is referred to as the lead. The lead provides an electrical pathway from the neurostimulator to the electrodes via the conductors that is isolated from the environment of the body. The lead must be designed to conform to the surrounding anatomy, to enable adequate modulation of neural tissue, to be biocompatible, and to be reliable throughout the lifetime of the device. Materials of the lead in contact with body tissues must be selected to minimize the inflammatory response due to the insertion of a foreign object into the body. Additionally, the lead design should minimize the invasiveness of the procedure and should consider the potential of lead removal from the body without damage or disruption of neural tissue.
The lead may be connected directly to the neurostimulator and, in some cases, may be connected to an extension which bridges the connections between the neurostimulator and the lead. The lead or extension is secured to the neurostimulator connector using set screws or spring-lock mechanisms. It is important to establish a secure electrical connection between the lead and device header as improper connections may lead to increases in system impedance that may affect the therapy delivered. In addition, non-ionic fluids should be used for wiping the lead, and connections should be dried since fluid in the connection may result in short circuit. A short circuit may cause stimulation at the connection site, intermittent, or loss of stimulation. Extensions are typically used between a DBS lead and the neurostimulator. If the neurostimulator needs to be replaced due to infection, battery replacement, or other reasons, the extension may be disconnected from the neurostimulator without having to handle the previously implanted lead. For SCS leads, several types of extensions are available that allow flexibility in the number and type of leads that may be connected to the neurostimulator for programming. For example, either one lead may be connected to a single extension, or two leads may be connected to a single bifurcated extension. Thus, using combinations of extensions, it is possible to place up to four leads in multiple locations connected to a single SCS device. Lead insulators are typically made out of a robust, biocompatible, and flexible material such as polyurethane or silicone rubbers. Percutaneous, cylindrical leads such as those used in SCS and DBS are designed to have blunt tips that reduce the likelihood of tissue damage during insertion and, in some cases, also help steer the lead into place.
The conductors, typically wires, within the lead may be arranged in a variety of different ways, including multilumen, where the conductors are placed side-by-side running parallel to each other (some SCS leads) and helical, multifilar, where the conductors are coiled into a long helix (DBS leads). The advantage of using coiled conductors is reduced stress and torsion during tension, bending and twisting, which reduces the likelihood of conductor fracture under these conditions. The lead conductors are typically made of corrosion-resistant materials, such as MP35N (a nickel alloy) or platinum. The conductors themselves may be individually insulated to prevent shorting. Materials for coating these conductor wires may include polytetrafluoroethylene (PTFE) or ethylene tetrafluoroehtylene (ETFE) which are both corrosion-resistant.
The electrodes deliver electrical stimulation and are the interface between the implanted system and the excitable tissue. The function of the electrodes is to provide sufficient current to activate or inactivate the target neural tissue, without causing significant damage to the electrode or surrounding tissue. Met- als such as platinum or platinum–iridium are typically used for electrodes. The shape of the electrode is designed to be appropriate to the target anatomy and achieve the desired spatial activation. Typical shapes include cylindrical electrodes (as in SCS percutaneous leads and DBS leads), or flattened electrodes which could be circular, oval, or rectangular with rounded edges such as those in SCS paddle leads. The number and spacing of electrodes on a lead is also related to the size of the target anatomy or the resolution required for targeting. Leads with small spacing between electrodes may be used to target anatomical sites with finer resolution, compared to leads with larger spacing between electrodes which may be selected for covering a larger area.
SCS lead complications
Implanted leads are subject to a variety of adverse environmental conditions including corrosion caused by bodily fluids and mechanical stresses caused by body movement, discussed further below. Therefore, mechanical failures are a common cause of re-operation in patients with implanted SCS systems, as is lead migration . Thus, the lead must be designed to avoid, to the extent possible within technical capabilities, both migration and breakage. Vertical or horizontal lead migration may result in a loss of proper paresthesia coverage and reduced therapy outcomes.
Various types of lead anchors may also be utilized to help reduce or minimize lead migration. The use of a soft silicone anchor versus a rigid anchor attached to the lead with silicone medical adhesive to prevent slippage is recommended. Solid anchors may result in fractured conductors at lower cycles of a bending fatigue test compared to the soft anchors which caused no failures at 1 million cycles . The anchor should be attached to the lumbodorsal fascia using a figure-of-8 non-absorbable suture to minimize tissue trauma; 2-0 non-absorbable suture is recommended, and ligatures should not be overtightened on the anchor or connector boot. If the anchor has a tail, the tip of the anchor should be pushed through the fascia to maximize the bend radius of the lead ( Figure 9.4 A ). Pushing the end of the anchor through the fascia may prevent fractures observed distal to the point of anchor where the lead exits from the deep fascia caused by increased stresses by the repeated bending motion of the spine . In some cases, such as when using the Medtronic Titan™ anchor, biomechanical testing has shown that it is not necessary to push the anchor through the fascia to obtain appropriate lead retention ( Figure 9.4 B). The anchor should be placed close to the midline near the spinous process to prevent lead movement caused by muscle contractions. However, it is important to note that there is no existing technology to anchor leads at the specific point of therapy delivery within the body. In current practice, anchors that are somewhat distant from the precise point of therapy delivery are utilized, meaning that the potential for migration of the lead at the delivery locus remains.
