Implantable Pulse Generators ‘Stimulate’ Medical Device Industry

In recent years, there has been great excitement about the
use of neuromodulation to treat a wide array of medical conditions and
diseases. The technology uses electrical signals to stimulate or block
different nerve impulses in the body and is adapted from technology used in
cardiac rhythm management. It holds promise for a variety of conditions,
including reducing or eliminating back pain, curing obesity, lowering high blood
pressure, and controlling diabetes without daily injections of insulin.

Advanced ceramic materials are playing an important role in
the technology and are poised to play an even greater one as these medical
devices flood onto the market to treat an increasing number of ailments.
Ceramic-to-metal brazed assemblies for hermetically sealed electrical
feedthroughs, piezocomposite materials that facilitate ultrasonic device
communication, and biocompatible ceramics as an alternative to titanium device
casings are just a few of the ways that advanced ceramics are playing a part in
enhancing this technology. These ceramic materials and technologies play an
important part in developing new and innovative treatment methods that were
simply not possible with traditional materials.

Research and development on new ceramic composite materials
and assemblies, as well as high pin density feedthrough assemblies, is being
pursued to enable a next generation of neuromodulation devices that will
provide better treatment, improved patient safety and convenience, and better
communication with other devices.

Implantable Pulse Generators—Key to the New Technology
Central to the technology is a neurostimulator, usually referred to as an
implantable pulse generator (IPG). The IPG is a battery-powered
micro-electronic device, implanted in the body, which delivers electrical
stimulation to the nervous system. An essential part of surgically implanted
systems designed to treat a wide array of conditions, the IPG delivers very small
pulses of electricity to block or stimulate nerve signals (or impulses),
depending upon the condition.

Figure 1: The different electrical feedthroughs (laser-welded to an IPG case) provide reliable transport of electrical signals from the IPG electronics hermetically sealed inside the case to the appropriate nerve locations to effect treatment of a patient.

Figure 1 shows an array of different electrical feedthroughs
that are laser-welded to an IPG case. They provide reliable transport of
electrical signals from the IPG electronics hermetically sealed inside the case
to the appropriate nerve locations to effect treatment.

In some cases, the devices are applied to conditions for
which medicines either haven’t been completely effective or have unpleasant
side effects. In other cases, nerve stimulation is looked at as a way to
control the condition more conveniently for the patient, either alone or in
combination with medicine. The payoff would be significant if a device could be
implanted in the body laparoscopically with only a very small incision. Imagine
a twenty minute outpatient surgery, followed by years of 100% patient
compliance, with no possibility of forgetting to take medication. The thought
has doctors, patients, and insurance companies very excited.

The Feedthrough—Hermetic
Structure Key to Success
One key component of the IPG devices is the feedthrough, the mechanical
structure that provides the electrical connection for the leads to get in and
out of the device housing.

This tiny component performs several key functions. First,
the feedthrough provides the conduit for communication of signals between the
IPG and the body. Second, the feedthrough’s hermetic seal keeps body fluids
outside the IPG device and prevents electricity and battery materials from
leaking out into the body. It must be completely and totally leak-free. It also
has to be robust enough to withstand radio frequency and eliminate interference
from MRI equipment and anti-theft scanners. This tiny piece of device real
estate can contain as few as two leads up to around thirty.

“The feedthrough
technology is changing rapidly, as next generation devices get smaller and more
compact and device designers seek to add more leads to improve the therapeutic
value of the devices,” says John Antalek, Morgan Technical Ceramics – Alberox
(MTC-Alberox) medical unit business manager.

Antalek says that many device manufacturers often start with
an off-the-shelf feedthrough to get their first generation device on the
market. Their next generation devices are much smaller and more compact, which
makes them more palatable to doctors and patients. “They also have a lot more
bells and whistles and customers come to MTC to obtain a customized feedthrough
that incorporates the additional features needed. Since we make our ceramic
components in house, we have developed manufacturing processes capable of
producing numerous sizes and shapes of feedthroughs to match the device design
needs.”

Stimulating from Head to Toe —Examples of IPG Applications
New medical uses for IPG devices are patented frequently. Among the conditions
for which the devices show the most promise are chronic back pain, hypertension,
and diabetes. Examples of devices focused on these conditions (either available
now or under investigation) follow.

Chronic back pain
IPG devices deliver mild electrical pulses to the spinal cord, which interrupt
or mask the transmission of pain signals to the brain. In this application, the
IPG is implanted in the back, in close proximity to the nerve that doctors are
trying to block.

Hypertension (high blood pressure)
Most patients with high blood pressure control the condition by using a regimen
of anti-hypertensive drugs. However, many studies have reported a persistence
of refractive hypertension (elevated blood pressure despite using at least two
anti-hypertensive drugs) in as much as 18% of the patient population. The IPG
devices are being developed to provide a new and improved therapy for treating
hypertension, which is not only safe and effective, but also, avoids
undesirable side effects of drug therapy. The system includes an IPG, sensors
and leads, external electronics for calibration, programming, and periodic
adjustment of parameters by the attending physician.

For example, one hypertension treatment clinical trial is
investigating whether an implanted device can help control high blood pressure
by stimulating pressure sensors called baroreceptors located on the carotid
artery and in the carotid sinus. These sensors measure and report blood
pressure to the brain, where it is compared to the needs of the body.

Another example involves investigations on a device that
stimulates the vagus nerve to control obesity; researchers testing the device
have seen a dramatic drop in hypertension as an unexpected benefit of the
therapy.

Diabetes
Several devices are being used or are under development, especially as an
option for patients with diabetes who have proven unresponsive to drug therapy.
An IPG is implanted and used to stimulate or inhibit the patient’s vagus nerve
to modulate its electrical activity to increase or decrease secretion of
natural insulin by the patient’s pancreas. The stimulator might be selectively
activated in response to direct measurement of blood glucose or symptoms or
could be activated automatically at predetermined times or intervals.
Alternatively, it could be automatically activated using an implanted sensor to
detect the blood glucose concentrations.

One implantable system, originally tested to control obesity
and other gastrointestinal disorders, is showing some promise in controlling
diabetes. The device is designed to precisely control nerve and organ function
using the vagal nerves, which regulate much of the activity of the stomach and
the pancreas. The device being studied delivers high frequency, low energy
electrical signals through laparoscopically implanted leads to block vagal
nerve transmission. The delivery of energy to the nerves is intermittent and
the effects of the therapy on the nerves and end organs are intended to be
reversible. The system is designed to be precisely programmed and noninvasively
adjusted to meet individual needs.

Headaches, obesity, epilepsy, depression, Parkinson’s,
syncope, sleep apnea, and restless leg syndrome are a few of the many other
conditions for which this treatment is being investigated.

Smaller but Better Devices with More Power and Features
The general trend in implantable devices is miniaturization. New devices tend
to be smaller, but with a greater number of leads that get more signals into
and out of a single device. It is clear that improving the feedthrough and
expanding capability is central to the next generation of IPGs. Future
neurostimulator applications are currently looking at 100 to 200 leads, which
will give device manufacturers opportunities to add further treatment options to
an implantable system.

“We know where the IPG device is headed and we want to
proactively provide improved feedthrough capabilities to help the device
manufacturers meet their needs,” says Antalek. “Just look at how far we’ve come
with cardiac rhythm management. Pacemakers were the size of a Blackberry just a
few years ago and had only two leads. Now the typical pacemaker is about the
size of a lighter and can have as many as 10 leads, some of which allow better
communication to the device, monitoring of other patient information, and the
ability to send information directly from the device to a doctor.”

Additional leads could also build in intentional redundancy,
which would reduce the device downtime and eliminate the need to remove the
device if any of the leads fail.

One of the most exciting avenues of research to increase the
number of leads is the development of new high density feedthroughs that could
contain ten times the number of leads, while keeping the current size and
spacing. Today’s feedthroughs are constructed by assembling many different
parts, stacking them into complicated arrays with braze materials, and putting
them in a furnace for joining. However, researchers are now developing high
density feedthroughs using cutting edge advanced ceramic materials and
processing technologies that use miniaturization techniques to pack many more
wires together in a much tighter space.

Body Communications
Another interesting development in the IPG arena is the development of “body
communications,” in which ultrasonic devices are placed into a medical device
casing and used to remotely power and communicate with other devices in the
body.

“This next level of improvement has great advantages,
because it could mean that no wires would have to be implanted,” notes Mark
Bartrum, transducer design manager for the ElectroCeramics business of Morgan Technical Ceramics (MTC ElectroCeramics). MTC ElectroCeramics uses its piezo
ceramic components (high density PZT and single crystal piezo materials) in
medical device manufacturing.

“Implanting wires in the body can be a challenge. They may
eventually fail and subsequent removal and replacement can be difficult. Also,
using ultrasound, as opposed to radio frequency, means the communication stays
within the body. This means one person’s medical device is less likely to
interfere with another person’s device and it could be more readily protected
against interference from MRI equipment, scanners, or other large electrical
devices.”

Using ultrasound to both power and interrogate remote
sensors is a likely development for many implantable devices, but wiring would
still be needed for neurostimulators, where leads are attached to the skull,
brain, or spine. However, in the future, the main implant might be able to
communicate with other devices implanted in the body or the external programmer
via ultrasound rather than radio frequency.

Another exciting development—the use of piezo ceramic
components—is an outgrowth from the technology used in cochlear implants. MTC’s
Bedford, Ohio
plant has researched a custom assembly that uses piezo ceramic components to
increase resolution for an annunciator that could be inserted into a main IPG and
use intelligible speech to warn the user that an event is occurring.

New Biocompatible Materials for IPGs
Most IPGs are currently made of titanium—a strong and light metal that is
lustrous and corrosion-resistant. However, along with efforts to improve the
basic electrical feedthroughs so more leads can be added, research and
development is being conducted using ceramic injection molding (CIM) to develop
a thin-walled ceramic case that could be smaller and simpler, while providing
more efficient communications to the device electronics. CIM enables production
of small components with very high precision without the need for a secondary
grinding process.

For example, MTC’s Stourport,
UK CIM facility
is currently in the early stages of developing an implantable housing for use
in migraine and cluster headache treatment that is made using Zirconia
injection molding. Zirconia is the preferred material for this device because
it has a high mechanical strength that allows the casing to be made with very
thin walls. The ceramic casing would then be brazed and hermetically bonded to
the feedthrough.

The Zirconia ceramic casing is stronger than titanium,
allowing for a mechanically robust structure in a smaller sized housing. By
comparison, an Alumina equivalent would be strong, but twice as thick. Both
Zirconia and Alumina are transparent to radio frequency energy, so signals
could be passed through the wall for communication and possible charging. The
hope is that developing a device casing out of Zirconia would mean that no
feedthrough wires would be needed to connect to an antenna. Keeping the antenna
within the device improves function for the patient. The Zirconia material is
also inherently insulating, so electrical wires can be placed closer together
than a metal flanged feedthrough brazed into a metal housing. Such a device
would have no need for a battery, so it would not require replacement, as long
as it retains its hermetic seal. Finally, the injection molded Zirconia is a
biocompatible material that complies with ISO 13356 implants for surgery.

Next Steps
The market for neuromodulation is estimated at more than $2 billion, with a
compound annual growth rate (CAGR) estimated at 18% to 22% and a seemingly
never-ending supply of new applications for the basic technology. With an
increasing acceptance by the FDA and insurance companies, preference over some
drug therapies, and increasing device complexity to deliver more features and
tailored effect, it is clear that developing the next generation of IPGs is
critical to advancing neuromodulation technology.

What is also clear is that advanced ceramics will be a major
part of that quest. The same robust biocompatible materials already being used
to make implantable drug delivery devices may now be used to develop a
feedthrough that will be used in next generation IPGs.

Chris Vaillancourt is new business development manager at
Morgan Technical Ceramics.