Optical imaging opens a new window on tuberculosis diagnosis

Optical imaging techniques could improve the accuracy of tuberculosis diagnoses and make it easier to gather evidence on the efficacy of new drugs or vaccines, according to research presented at the World Molecular Imaging Congress in Nice.

TB kills over two million people a year, predominantly in developing countries. One-third of the world's population is currently infected with the pathogen. Efforts to combat the disease are being hampered by strains that are resistant to several antibiotics used to treat TB. Highly infectious TB sufferers go untreated owing to difficulties confirming the diagnosis promptly.

The most widely used methods of imaging TB are x-ray radiography and PET/CT, but neither modality is specific enough to make a firm diagnosis. Suspected diagnoses of TB can be confirmed with laboratory tests of the patient's saliva. Current methods take at least 15 days to yield a result, however, and require an expert microscopist to interpret the findings.

Researchers from the Texas A&M Health Science Center in the U.S. believe that molecular optical imaging strategies could provide a faster, more specific way to identify TB. These methods could be used in drug development studies and, in some cases, for the diagnostic imaging of patients as well. Studies of several different techniques have identified two promising candidates that could be appropriate for clinical use, according to Jeffrey Cirillo, Ph.D., an associate professor in the department of microbial and molecular pathogenesis at Texas A&M.

The favored strategies are sequential reporter enzyme luminescence and reporter enzyme fluorescence. Both methods use catalytic enzymes produced by TB bacteria to amplify the signal far beyond standard bioluminescent or fluorescent systems.

"It's amazing how sensitive these systems are. With amplification methods, a fluorescent probe can build up almost indefinitely in an organ so you can get a very bright signal," he said.

The proposed optical systems have several advantages over alternative molecular imaging methods, such as PET or SPECT, for imaging TB, Cirillo said. The imaging equipment and the facilities to produce short-lived radioisotopes may be beyond the budgets of local healthcare centers in developing countries, where TB is most rife.

"One problem with nuclear medicine techniques is that they are very expensive," he said. "We are trying to get something that will be cost-effective for the developing world, something that is more low-tech."

Many of the probes being trialed in the optical imaging studies are stable at room temperature. They will need to be tested for toxicity prior to human use. Researchers will also need to find a good method of delivery, Cirillo said.

"For the developing world, we would prefer oral administration and getting patients to drink something, so we don't have to use needles," he said.

A viable setup for imaging human subjects will also have to be developed. Putting a mouse in a dark box is one thing. But asking patients to walk into a dark enclosure and stay there for 15 minutes could be another matter altogether.

In the meantime, team members are preparing to validate their optical methods of TB diagnosis on clinical samples and compare the results against existing techniques.

"We are going to make sure that this works very well and is specific. Then we can move on to developing systems," Cirillo said.

-By Paula Gould