To understand the brain and its chemical complexities, researchers would like to peer inside the skull and observe neurotransmitters at work. Unfortunately, research methods to measure levels of certain chemicals in the brain require drilling holes in the skull, and noninvasive imaging techniques, such as MRI, can’t detect specific molecules. Now, as a first step toward a new imaging tool, researchers have shown that they can use Raman spectroscopy todetect chemical signatures through bone (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja409378f).
With Raman spectroscopy, chemists can look for chemicals of interest sitting inside a range of materials, such as explosives inside plastic bottles. Richard P. Van Duyne’s group at Northwestern University has used the technique to monitor glucose levels through the skin of living rats (Anal. Chem. 2011, DOI: 10.1021/ac202343e).
To peer through bone, Sharma and colleagues combined two spectroscopic techniques: surface-enhanced and spatially offset Raman spectroscopy. Both methods involve exciting samples with laser light and then monitoring for specific Raman signals from the sample that are characteristic of a chemical of interest.
In the surface-enhanced variety, gold nanoparticles boost the Raman signal produced by molecules bound to their surfaces. The spatially offset method allows researchers to detect a useful signal from molecules located up to 20 mm within a sample. Researchers can isolate signals from these buried compounds by observing Raman signals at a different spot from where they shine the laser light. The separation ensures that the molecule’s signal isn’t dwarfed by scattered laser light from the sample’s surface.
As a test of the combination method, the researchers went to the market and bought a cut of lamb shoulder with a bone 3 to 8 mm thick. The human skull is 3 to 14 mm thick. The team then injected 90 trillion gold nanoparticles into the meat behind the bone. They had decorated the particles with a compound that has a strong Raman signature. When they shined 785-nm laser light on the bone, they could immediately detect the chemical signature of the reporter molecule. Sharma jumped up and down when she saw the results. “Everything I read and everyone we talked to said, ‘No, this shouldn’t work,’” through bone because the material isn’t transparent enough, Sharma says.
Right now the researchers cannot detect where the nanoparticles are located within the tissue, Van Duyne says, only that they are on the other side of the bone. And even with further refinements, the depth of tissue penetration is likely to be limited to areas close to the tissue’s outer surface.