Tiny robots could help surgeons remove
hard-to-reach brain tumors, say researchers.
A robot that worms its way in
The median survival rate for patients with
glioblastomas, or high grade primary brain cancer, is less than two years.
One factor contributing to this low rate is the fact that many deep-seated and
pervasive tumors are not entirely accessible or even visible when using current
neurosurgical tools and imaging techniques.
But several years ago, J. Marc Simard, M.D., a
professor of neurosurgery at the University of Maryland School of Medicine in
Baltimore (UMB), had an insight that he hoped might address this problem. At
the time, he had been watching a TV show in which plastic surgeons were using
sterile maggots to remove damaged or dead tissue from a patient.
"Here you had a natural system that recognized
bad from good and good from bad," said Simard. "In other words, the maggots
removed all the bad stuff and left all the good stuff alone and they're really
small. I thought, if you had something equivalent to that to remove a brain
tumor that would be an absolute home run."
And so Simard teamed up with Rao Gullapalli,
Ph.D., professor of diagnostic radiology and nuclear medicine also at UMB, as
well as Jaydev Desai, Ph.D., professor of mechanical engineering at the
University of Maryland, College Park, to develop a small neurosurgical robot
that could be used to remove deep-seated brain tumors.
Within four years, the team had designed,
constructed, and tested their first prototype, a finger-like device with
multiple joints, allowing it to move in many directions. At the tip of the
robot is an electrocautery tool, which uses electricity to heat and ultimately
destroy tumors, as well as a suction tube for removing debris.
"The idea was to have a device that's small but
that can do all the work a surgeon normally does," said Simard. "You could
place this small robotic device inside a tumor and have it work its way around from
within, removing pieces of diseased tissue."
A key component of the team's device is its
ability to be used while a patient is undergoing MRI. By replacing normal
vision with continuously updated MRI, the surgeon is able to visualize
deep-seated tumors and monitor the robot's movement without having to create a
large incision in the brain.
In addition to reducing incision size, Simard
says the ability to view the brain under continuous MRI also helps surgeons
keep track of tumor boundaries throughout an operation. "When we're operating
in a conventional way, we get an MRI on a patient before we do the surgery, and
we use landmarks that can either be affixed to the scalp or are part of the
skull to know where we are within the patient's brain. But when the surgeon
gets in there and starts to remove the tumor, the tissues shift around so that
now the boundaries that were well-established when everything was in place
don't exist anymore, and you're confronted once again with having to
distinguish normal brain from tumor. This is very difficult for a surgeon using
direct vision, but with MRI, the ability to discriminate tumor from non-tumor
is much more powerful."
Steve Krosnick, M.D., a program director at
NIBIB, says real-time MRI guidance during brain tumor surgery would be a
tremendous advantage. "Unlike pre-operative MRI or intermittent MRI, which
requires interruption of the surgical procedure, real-time intra-operative MRI
offers rapid delineation of normal tissue from tumor while accounting for brain
shifts that occur during surgery."
But designing a neurosurgical device that can be used inside an MRI magnet is
no easy task. One of the first issues you have to consider, said Gullapalli, is
a surgeon's access to the brain. "When you scan a person's brain during an MRI,
he's deep inside the machine's tunnel. The problem is, how do you get your
hands on the brain while the patient's in the scanner?"
The team's solution was to give the surgeon
robotic control of the device in order to circumvent the need to access the
brain directly. In other words, a surgeon can insert the robot into the brain
while the patient is outside of the scanner. Then, when the patient moves into
the scanner, the surgeon can sit in a different room and -while watching MRI
images of the brain on a monitor—move the robot deep inside the brain and
direct it to electrocauterize and aspirate the tissue.
Jaydev Desai, the team's mechanical engineer,
says the most challenging aspect of the project has been designing a robot that
can be controlled inside the magnetic field of an MRI. While robots are often
controlled via electromagnetic motors, this was not an option because, besides
being magnetic, these motors create significant image distortion, making it
impossible for the surgeon to perform the task. Other potential mechanisms such
as hydraulic systems were off the table due to concerns about fluid leakage.
Instead, Desai decided to use shape memory alloy
(SMA)—a material that alters its shape in response to changes in temperature—to
control the robot's movement. In the most recent prototype—developed by Desai
and his team at the Robotics, Automation, and Medical Systems (RAMS) laboratory
at the University of Maryland, College Park—a system of cables, pulleys and SMA
springs are used. This cable and pulley system is an improvement from their
previous prototype which caused some image distortion.
With continued support from NIBIB, Desai and
colleagues are now working to further reduce image distortion and to test the
safety and efficacy of their device in swine as well as in human cadavers.
Though it will be several years before their device finds its way into the
operating room, Simard is excited by the prospect. "Advancing brain surgery to
this level where tiny machines or robots could navigate inside people's heads
while being directed by neurosurgeons with the help of MRI imaging...It's beyond
anything that most people dream of."
Scoping the brain
On the opposite side of the country, a different
group of engineers and neurosurgeons is also working to develop an
image-guided, robotically-controlled neurosurgical tool. Lead by Eric Seibel,
Ph.D., a professor of mechanical engineering at the University of Washington,
the team is attempting to adapt a scanning fiber endoscope—a tool initially developed
by Seibel to image inside the narrow bile ducts of the liver—so that it can be
used to visualize the brain during surgery.
An endoscope is a thin, tube-like instrument with
a video camera attached to its end that can be inserted through a small incision
or natural opening in the body to produce real-time video during surgery.
Endoscopes are an essential component of minimally invasive surgeries because
they allow surgeons to view the inside of the body on a monitor without having
to make a large incision.
However, there are many parts of the body such as
small vessels and ducts as well as areas deep in the brain that are
inaccessible to conventional endoscopes. Although ultrathin endoscopes have
recently been developed, Seibel says these smaller scopes come with the price
of greatly reduced image resolution.
"Right now, with the current state of the art
ultrathin endoscopes, I calculate based on the field of view and their
resolution that the person looking at that display would see so little as to be
classified in the US as legally blind," said Seibel.
But with support from NIBIB over ten years ago,
Seibel began working on a new type of endoscope that could fit into tiny
crevices in the body while retaining high image quality. His end product was a
new type of endoscope that, despite having the diameter of a toothpick, can
provide doctors with microscopic views of the inside of the body.
Seibel retained image quality while significantly
reducing the size of his scope by eschewing traditional endoscope models.
Instead of a light source and a video camera, Seibel's scope consists of a
single optical fiber—approximately the size of a human hair—located in the
middle of the scope. The fiber releases white laser light (a combination of
green, red, and blue lasers) when vibrated at a particular frequency. By
directing the laser light through a series of lenses in the scope, it can be
reflected widely within the body, providing a 100 degree field of view. As the
white laser light interacts with tissue, it picks up coloration and scatters it
back to a ring of additional optical fibers which transmit this information to
"It's almost like putting your eyes inside the
body so you can see with the wide field view of your human vision," said
In collaboration with three neurosurgeons and an
electrical engineer, Seibel is now working to secure his novel endoscope to the
tip of a robotically controlled micro-dissection neurosurgical tool.
As opposed to larger traditional endoscopes,
Seibel say his scanning fiber endoscope is barely noticeable.
"It' s like a piece of wet spaghetti," said
Seibel. "It's even smaller then a piece of wet spaghetti in diameter, but it
feels like that. So when it is actually at the tip of the surgeon's tool, the
surgeon wouldn't feel it dragging behind her."
One advantage of having the endoscope under
robotic control is that the brain can be imaged at a higher magnification.
"A surgeon couldn't hold a microscope steady in
her hand while performing surgery, but the robot can," said Seibel.
Microscopic detail is essential when trying to determine the border between
healthy tissue—which if removed could lead to neurological deficits—and
cancerous tissue—which if left in the brain could allow a tumor to return.
Krosnick says he's excited by the combination of
high-quality imaging and robotic enabled micro-neurosurgery. "It addresses a
critical need, which is to discern tumor margins at high resolution while
minimizing disruption to normal structures."
Seibel believes this discrimination between
cancerous and healthy tissue could be enhanced even further by taking advantage
of the fact that his scanning endoscope is also able to detect fluorescence.
One of the main focuses of his current research is a collaboration with Jim
Olson, M.D., Ph.D. at the Fred Hutchinson Cancer Research Center, who is the
inventor of a substance called "tumor paint".
Tumor paint is a fluorescent probe that attaches
to cancerous but not healthy cells when injected into the body. Seibel says the
ultimate goal would be to give a patient an injection of tumor paint and then
use his endoscope to create an image of the fluorescing cancer cells as well as
a colored anatomic image of the brain. The two images could then be merged on a
screen for the surgeon to view during an operation."You would be able to see
all the structure that a surgeon would see, but you'd also see those molecular
pinpoints of light that are cancer cells...and from there the robot can be used
to resect, or remove, these small cells of cancer, and it can do it very
precisely because you don't have the shaking of a human holding it."
Seibel concluded by saying, "There's a real niche
for video-quality, high-resolution, multi-modal imaging that's in a tiny
package so that it can be put on microscopic tools for minimally invasive
medicine. I really feel it's an enabling technology that could move the whole
Krosnick is enthusiastic about the progress the two
teams have made so far. "These are innovative technologies that, if effective,
could significantly add to the brain surgery armamentarium. They're still early
in development, but I think both show considerable promise." He concluded by
emphasizing that, like all new devices, these technologies would need to
undergo a series of clinical trials to ensure that they are safe and effective
before making their way into an operating room.