Ultrasound extends the reach of fluorescence imaging

Ars Technica : Fluorescence imaging entails illuminating specially tagged molecules with laser light and then detecting the fluorescent emission that results. Thanks to its molecular specificity, the technique has proven invaluable for studying single cells and small samples. But its usefulness for imaging thick samples, such as human organs, is limited because light is easily scattered in opaque media. Now, Meng Cui of the Howard Hughes Medical Institute’s Janelia Farm research campus and his colleagues have developed a way to overcome that limitation—by using ultrasound. First, they focus synchronized laser pulses and ultrasound pulses at a point of interest inside the sample. The ultrasound shifts the frequency of the laser light that scatters back out from the focus. By measuring the frequency-shifted wavefront that emerges from the sample, the researchers—or, rather, their algorithm—can determine what a fluorescent signal would look like if it originated at the same point. To make a fluorescence image, they step through the sample, targeting each point with the laser–ultrasound combination and using the frequency-shifted signal to reconstruct the location of any fluorescent molecules. In a paper in Nature Photonics, Cui and his colleagues reported being able to resolve structures on the order of tens of microns in size and at depths of a few millimeters.