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Augmented microscopy to aid tumor resection

03 Dec 2015

Combination of imaging technologies gives surgeons a 3D view of tumors and blood flow.

by Ford Burkhart in Tucson
In a development that promises to aid vascular and brain tumor surgeons, University of Arizona (UA) bioengineers have developed a novel microscope that combines two images of tissue in a single view – the optical image overlaid with a fluorescence image from dye attached to tiny structures in cells.

The two views are blended into a single, color, 3D image in real time, analogous to the way that traffic and other information is overlaid onto Google Maps.

The new device is expected to play an important role aiding surgeons operating on blood vessels and differentiating tumors from normal tissue during brain cancer resections. Crucially, the “real-time” aspect will avoid any delay that might otherwise be required to look away from the microscope.

Known as “augmented microscopy”, the technology is working its way towards the marketplace through the UA campus intellectual property channels, says Marek Romanowski, project leader at the BIO5 Institute and the UA Cancer Center.

Surgeons helped develop the new scope to provide them with functional information on top of what the eye sees of the anatomy. “The great breakthrough is its user-friendly fashion,” said Jennifer Barton, interim director of BIO5. “You don’t have to turn off the lights. There’s no awkward equipment. They found a way to work in the normal environment and still provide information that is critical to patency (blood flow) of vessels or the margins of a tumor.”

One big technical hurdle, explains Romanowski, is that a human’s 3D perception relies on principles very different from electronic imaging. “Merging these two concepts is not trivial,” he said.

“But surgeons desperately need the 3D vision as they cut through tissue, so we had to provide the optical 3D image, and add the electronic image to it,” he said. “You would lose the optical image using the purely electronic pathway. We retained the optical and added the electronic.”

The approach helps resolve problems known as accommodation distance and convergence angles. “In the normal vision of the surgeon, these two aspects always agree,” Romanowski said. “Go to fully electronic vision and you lose that perfect agreement.”

With aid of a marker dye, for example indocyanine green, which is injected into patients, the device provides sharp images to visualize blood flow. It borrows the concept of merging real (bright-field) and synthetic images from the graphic display technology - known as “augmented reality”.

The team is now focusing on ways to extend its capabilities to provide augmented images of brain tumors.

Clinical trials
Built inside a small box that fits inside a surgical microscope, the device is currently restricted to laboratory studies on animal models, and awaiting regulatory approval for clinical trials. Tests on human subjects are expected within the next year, pending availability of funding.

The university would likely turn the technology and its marketing over to a commercial partner through a licensing agreement with a small start-up or a company that already sells microscopes with existing cameras that create a video loop of tissue, UA team members said.

Romanowski suggests that the imaging technique is analogous to a Google map that overlays roads, traffic and boundary information on top of the physical surface features. In an augmented microscope, the extra information appears over the tissue surface instantly. “It is as if the tissue was painted to help direct the surgeon's work,” he said. “They provide the illusion of one image.”

His lab team has been working on augmented microscopy for about five years at the BIO5 Institute, which brings together multidisciplinary teams from medicine, engineering, pharmacology, agriculture and science.

Two years ago, the BIO5 team connected with UA surgeons who saw the augmented microscope’s potential for difficult surgery within the skull, where precision vision is critical.

Real-time overlay: a big step forward
One of those surgeons was Dr. G. Michael Lemole Jr., chief of neurosurgery at the UA College of Medicine. A specialist in brain tumor surgery, he co-authored two recent research papers on the device with Romanowski.

"The big step forward is “the real-time overlay," said Lemole. “You can see the changes in blood flow right on the anatomy.” To apply the device to a tumor, you would take the indocyanine green that reveals the activity in blood vessels and bond it to something that would be taken up by the tumor. That is the step now under development.

More than 20,000 new cases of primary brain cancer are diagnosed in the US each year, while nearly 16,000 patients die from the disease, Romanowski said. Of the half-million patients who die of any other cancer, up to a third have some form of the disease that spreads to the brain.

The new UA technique could have applications outside of cancer surgery. It holds particular promise for aneurysm - the bulging of blood vessels caused by weakened arterial walls. Neurosurgeons currently treat an aneurysm by sealing it off from connecting vessels, to prevent a rupture. Nearly half of patients with ruptured aneurysms die, Lemole said, and at least half the survivors have major mobility and other problems.

In addition to its new features, the augmented microscope provides real-time magnification and focus adjustments, camera mounting, and multi-user access, comparable to standard surgical microscopes.

• For more technical detail on the device, see: “Augmented microscopy: Real-time overlay of bright-field and near-infrared fluorescence images,” published in the October 2015 edition of SPIE’s Journal of Biomedical Optics.

About the Author

Ford Burkhart is a writer based in Tucson, Arizona.

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