A new medical imaging breakthrough is on the horizon that will assist doctors to see what is happening inside a living body. Previously, this ability has been hampered by the various limits on detecting tiny components of living, breathing, internal bodily structures and events.
Now a team of researchers at the Stanford University School of Medicine (Stanford, California) has developed a system that can illuminate tumors in living subjects — getting pictures which they say have a precision of nearly one-trillionth of a meter.
This technique, called Raman spectroscopy, expands the available toolbox for the field of molecular imaging, said team leader Sanjiv Sam Gambhir, MD, PhD, professor of radiology at Stanford. He is the senior author of a study describing the method, published in the March 31 issue of the Proceedings of the National Academy of Sciences.
"This is an entirely new way of imaging living subjects, not based on anything previously used," said Gambhir, who directs the Molecular Imaging Program at Stanford. He said signals from Raman spectroscopy are stronger and longer-lived than other available methods, and that the type of particles used in this method can transmit information about multiple types of molecular targets simultaneously.
"Usually we can measure one or two things at a time," he said. "With this, we can now likely see 10, 20, 30 things at once."
Christina Zavaleta, one of the co-first authors of the study, expanded on the Raman effect for Medical Device Daily.
"Raman has been used in biomedical applications for several years, particularly when surface-enhanced Raman scattering was first discovered in 1979. [This] results in high Raman intensities of up to 1,014, which are much easier to identify. We are using this technique because it is ultra-sensitive — 8 picoMolar — in detection," she said.
"For instance, if we injected a 20 micro liter volume just under the skin of a mouse, then with the surface enhanced Raman spectroscopy [SERS] nanoparticles there only needs to be about 100 million of these particles in that volume in order to see them with our Raman microscope. On the other hand, it takes 100 billion quantum dots [1,000 times more particles] in that 20 micro liter volume in order to detect them with current optical imaging devices [IVIS and Maestro].
"So our Raman microscope, in conjunction with SERS nanoparticles, is 1,000 times more sensitive than these optical imaging devices in conjunction with quantum dots. All in all, this means that we don't need as many of these SERS nanoparticles to get to and target the tumor site in order for us to be able to detect it."
Gambhir said he believes this is the first time Raman spectroscopy has been used to image deep within the body, using tiny nanoparticles injected into the body to serve as beacons. When laser light is beamed from a source outside the body, these specialized particles emit signals that can be measured and converted into a visible indicator of their locations in the body.
Gambhir compared the Raman spectroscopy work to the development of positron emission tomography discovered 20 or 30 years ago. PET has become a routine hospital imaging technique that uses radioactive molecules to generate a three-dimensional image of body biochemistry.
"Nobody understood the impact of PET then," he said, referring to that discovery. "Ten or 15 years from now, people should appreciate the impact of this."
Will this spectroscopy be used specially on cancerous tumors, or will its use eventually branch out into other applications?
Asked this question, Zavaleta told MDD, "We are concentrating our efforts towards in vivo cancer detection with SERS nanoparticles; however, Raman spectroscopy is in no way limited to cancer applications. For instance, it has already shown to be effective in characterizing/classifying atherosclerotic plaques [Feld Group, MIT. J Biomed Opt. 2006 Mar-Apr;11(2):021007] and even used to evaluate mineral components in enamel, dentin, and calculus, and calcium fluoride formed in/on enamel in dental research [TSUDA H. Eur J Oral Sci. 1996 Apr;104(2(Pt 1):123-31].
"The applications are unlimited because of Raman's unique ability to characterize chemical components by the inelastic scattering of light from any material."
As part of this proof-of-principle work, Gambhir's team tagged the gold nanoparticles with different pieces of proteins that honed in on different tumor molecules.
"We could attach pretty much anything," said Gambhir.
The Raman effect also lasts indefinitely, so the particles don't lose effectiveness as indicators, as long as they stay in the body.
Using a microscope the researchers modified to detect Raman nanoparticles, the team was able to see targets on a scale 1,000 times smaller than now obtainable by the most precise fluorescence imaging using quantum dots.
When adapted for human use, they said, the technique has the potential to be useful during surgery, for example, in the removal of cancerous tissue. The extreme sensitivity of the imager could enable detection of even the most minute malignant tissues.
Gambhir's lab is further studying these Raman nanoparticles to follow their journey throughout the body over the course of several days before they are excreted. They are also optimizing the particle size and dosage, and are evaluating the particles for potential toxicity.
Gambhir also is publishing a study in the March 30 issue of Nature Nanotechnology indicating that the carbon nanotubes are not likely toxic in mice.
The researchers said a clinical trial is planned to test the gold nanoparticles in humans for possible use in conjunction with a colonoscopy to indicate early-stage colorectal cancer.