Imagine an exam that combines into a single scan the diagnostic imaging power of 10 PET studies, each measuring an essential dimension of cancer's aggressiveness, metastatic potential, and susceptibility to radio- and chemotherapy.

That day may arrive soon thanks to the inventive work of Dr. Sanjiv Sam Gambhir's molecular imaging laboratory at Stanford University. Its creative use of in vivo Raman spectroscopy promises to add “multiplexing” to the everyday language of imaging practice.

Raman spectroscopy, a sophisticated quantum physics technique that produces huge bursts of molecular excitation, earned its discoverer, Sir Chandrasekhara Venkata Raman, a Nobel prize for physics in 1930. Commonly used in chemistry, it is also applied in medicine to monitor anesthesia and respiratory gas mixtures during surgery. Its application in in vivo medical imaging is new, however, Gambhir said in an interview.

Raman spectroscopy uses a dual-component probe to target relevant physiology and produce a recordable signal. FDG, for example, accumulates in cancer cells, where it is phosphorolated and metabolized. Fluorine-18 radioisotope produces a positron signal that a PET scanner detects and localizes.

In Raman imaging, the localizing mechanisms are similar to those used in nuclear medicine, but the signaling mechanism is unique. A specific array of molecules is attached to gold nanoparticles. When the nanoparticle is excited with light, most of the photons elastically scatter at the same output frequencies as the input frequencies. With Raman scattering, however, some light is inelastically scattered, Gambhir said. The gold nanoparticles and their Raman layers amplify the inelastic scattering, so far more photons than normal are inelastically scattered.

As a result, the return signal is sharp and easily detectible. The signal amplification is huge, as is the signal-to-noise ratio, because background tissue produces little noise. Tissues where the Raman particles migrated because of their engineered targeting mechanism are amplified by the inelastically scattered light to produce an image.

In terms of multiplexing, Raman spectroscopy puts all medical imaging modalities preceding it to shame. With advanced energy windowing, SPECT imaging has simultaneously mapped the distribution of two radiopharmaceutical probes, such as thallium-201 and technetium-99m sestamibi. But the Stanford group's latest Proceedings of the National Academy of Sciences paper describes the simultaneous display of 10 types of targeted Raman particles simultaneously. And there is no technical reason why Raman spectroscopy will not eventually multiplex many times that number, Gambhir said.