Tiny scope finds difficult cancers deep inside the body

Confocal microscopes can generate high-resolution images of hard to reach organs in real time, and spot cancer at a curable stage.

Harry Aslanian, MD, Priya Jamidar MD, and Uzma Siddiqui, MD, work together to interpret images that are 1,000 times magnified.

(July 2010) When Harry Aslanian, MD, first looked at the images produced by the confocal laser microscope—one of the tiniest microscopes in the world—he saw what no one had seen before in real time in the pancreas: stunning, high-resolution images of active cells, individual red blood cells within vessels, and scar tissue 1,000 times magnified.

Attached to the tip of a long, thin, flexible probe, inserted through the stomach wall by way of a needle under endoscopic ultrasound guidance, the microscope sent back amazing pictures of an organ that is notoriously difficult to reach, and tricky to evaluate even by CT scan or MRI.

“The quality was quite good,” says Aslanian, associate director of endoscopy for Yale Medical Group, who performed the world’s first confocal laser endoscopic visualization of the interior of a pancreatic mass last year. He has done several similar procedures since then. Previous views of the pancreas showed only its overall texture, without any clues to cellular and subcellular activity. “Now we’re in the process of fine-tuning this, making a road map—asking, when you see this, what does it really mean?”

A way to spot cancer earlier

Confocal microscope probes with high resolution have been used in the past primarily as research tools. They evolved from what Aslanian describes as “tabletop versions,” to scopes that measure under 3 millimeters—roughly the thickness of a paper clip.

The microscope fits through the biopsy channels of many endoscopes—lighted optical instruments used to look deep inside the body to spot cancers and pre-cancers at their earliest stages of development, when many are curable.

Pancreatic cancer can form in solid tumors or cysts, and Aslanian is interested in using confocal microscopy to diagnose precancerous cysts, which can be surgically removed. “The potential for the microscope is that we can look at the cells in real time and possibly identify the ones that are likely to progress to cancer,” Aslanian says.

Yale Medical Group doctors in the Yale Interventional Endoscopy Program are also using the microscope to look inside the colon, bile duct and esophagus. They are are using the fiber optic, probe-based Confocal Laser Endomicroscope manufactured by Mauna Kea Technologies’ in Paris. Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven are among only a handful of institutions in the world with the technology and the only centers in the state using the confocal endomicroscopy.

A breakthrough for Barrett’s

Jamidar, right, discusses one patient's results with Siddiqui and Aslanian. Real-time images are very similar to what a pathologist would see under a microscope.

While Aslanian is still testing the microscope in clinical trials, the Food and Drug Administration has already approved its use for gastrointestinal endoscopy. Uzma Siddiqui, MD, director of Endoscopic Ultrasound at Yale Medical Group, has used it to examine patients with Barrett’s esophagus, which is associated with long-term esophageal reflux disease and can be a precursor to esophageal cancer.

Siddiqui says the microscope probe helps her target the most suspicious areas of dysplasia, or precancerous tissue changes. “The images you see in real time are very similar to what a pathologist sees under a microscope,” she says. Endoscopic ultrasound can further stage early cancers and, if indicated, the tissue can be removed by endoscopic surgery.

Doctors can use confocal endomicroscopy to make a precise diagnosis of Barrett’s and dysplasia and identify tissue that might otherwise be missed. Siddiqui performs another nonsurgical endoscopic technique called radiofrequency ablation that uses heat energy to remove Barrett’s tissue without damage to normal underlying structures.

Less invasive for patients

Jamidar, who is using confocal microscopy in the bile duct, believes it will improve diagnosis and therapy.

Meanwhile, Priya Jamidar, MD, director of Endoscopy at Yale Medical Group, is using confocal microscopy in the bile duct, where tissue sampling techniques are at best, 50 percent sensitive. This means that around half of tumors cannot be diagnosed at the time of examination. Yale has the most experience of any center with the use of the high-resolution probe in the bile duct, and Jamidar believes the new technology may improve diagnosis and help guide therapy.

Like Aslanian, Jamidar is still learning about acquiring and interpreting images. But he says there seem to be no harmful effects so far, and the microscope provides so much information that patients don’t need as many biopsies. “It’s an impressive technology that is much less invasive for our patients,” Jamidar says.