Researchers at Duke University, Durham, N.C., say they've developed a microscope with the depth and resolution that lets them peer so deep into living tissue they can see molecules interacting. They say the device combines tightly focused heat with optical coherence tomography (OCT). Such a microscope could let doctors inspect the margins of a tumor as it is removed from a body or assess effects of anticancer agents on blood vessels that nourish tumors.

High-resolution molecular imaging has been limited to relatively shallow penetrations that can be accessed with conventional microscopy. OCT is an optical analogue to ultrasound with relatively good penetration depth (1 to 2 mm) and resolution (about 1 to 10 µm). “We have developed a photothermal OCT as a molecular-contrast mechanism that allows for high-resolution molecular imaging at deeper penetration depths than microscopy,” says Duke Professor Joseph Izatt. ”Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps the focused spot of the sample arm of a spectral-domain OCT microscope.” Validation experiments in material similar to human tissue containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 ppm.

Recent experiments used the technique to view cells showing particular molecular receptors. “This technique could augment traditional methods of deep-tissue molecular imaging with a relatively high resolution,” says Melissa Skala, a colleague working with Izatt.