New tools from MGH use light to find microscopic traces of disease deep inside the body.
In the 1966 science-fiction feature, Fantastic Voyage, a submarine and its crew are shrunk to miniature size and embark on a harrowing journey through the human circulatory system. Buffeted by red blood cells, they get a microscopic view of a patient’s heart, ears, and lungs before successfully removing a life-threatening blood clot from deep in the brain.
Forty years later, we still don’t have miniature doctors, but researchers are working on the next best thing. One lab at Massachusetts General Hospital’s Wellman Center for Photomedicine is developing tiny, high-resolution optical endoscopes to send physicians on a different type of voyage into the body, one yielding microscale close-ups of hidden, and possibly diseased, tissues. One of the group’s latest devices is the smallest endoscope yet developed: it consists of a single optic fiber, hardly the width of a human hair, that can be threaded into tight cavities in the body and send back high-resolution, three-dimensional images of, for example, small tumors.
Medical imaging brings together physics and biology, which might explain why the MGH lab, one of the leaders in the field, is a joint effort. Brett Bouma, a physicist, and Guillermo “Gary” Tearney, a pathologist, share an office, a lab, and a conviction that the potential of light-based medical imaging has barely been tapped.
Unlike other techniques such as MRIs, X-rays, CAT scans, or ultrasound, light-based imaging can deliver three-dimensional images in microscopic and even molecular detail, and in real time.
“It’s ridiculous how much information can be carried with light,” Bouma says. “With our eyes, we can see the difference between red and blue, but if you measure carefully, light can have a million different colors between those two.” The ability to split a beam of light into an almost unlimited number of wavelengths allows a single optic fiber to carry the equivalent of all fax transmissions between the U.S. and Europe. Bouma and Tearney are taking advantage of this property for medical imaging.
A big drawback of seeing cells close up is that the view covers only a limited area. Finding trouble spots, such as a small tumor in a large organ, by imaging one area at a time can be like looking for a needle in a haystack.
Bouma and Tearney conquered that problem recently. They’ve developed a two-millimeter-wide endoscope that sweeps tissues with a beam of light that changes color constantly. Each wavelength strikes a different area, allowing the researchers to rapidly collect data on millions of tiny spots. In three seconds, they can scan an entire human coronary artery for plaque. Looking for cancer in the esophagus takes about two minutes. The techniques and instruments are now being tested in patients. The aim is to develop a system for the early diagnosis of heart disease or cancer.
Two in one
Still, sometimes a picture is not enough, and doctors need an actual piece of tissue to make a molecular-level diagnosis. Often that entails a biopsy, in which a technician guides a hollow needle to the site of a tumor and aspirates a sample of cells for further study. The technician knows, based on ultrasound or another low-resolution imaging technique, the approximate location of the cells of interest. But in one-third of the cases, the needle misses its mark and retrieves the wrong cells.
To solve this problem, Tearney and Bouma are working on a smart biopsy needle. As the needle passes through tissue, an optic fiber inside the needle transmits information back to the doctor, such as whether the tissue is muscle or tendon, or a suspected tumor. When the needle hits the target area, the operator can aspirate with greater confidence.
Eventually, imaging may provide diagnostic information even without a biopsy, says Bouma. He and Tearney are developing ways to use light to measure the chemical composition and structure of tissues in situ. That could even include “seeing” tissues at the molecular level, analyzing protein structure or DNA sequences. “There is a long future for research in this area,” says Bouma. Light has been underutilized, and there’s a lot to do.”