Super-resolution imaging has helped researchers get pictures of microscopic blood vessels in the brain of a live rat using ultrasound, researchers say.
Such research could one day help investigate diseases that modify blood vessels, such as cancer, stroke and thickening of artery walls in the heart and elsewhere, scientists add.
Current techniques for imaging microscopic blood vessels in living organisms are limited by how deep they can penetrate into tissues, the speed with which they can take pictures, and the resolution of the images they can capture. Although conventional medical ultrasound can image both deeply and quickly, it has, at best, offered a resolution of several hundred micrometers. Because waves diffract or spread out as they move, one consequence is that waves of radiation such as ultrasound cannot be used to directly image features smaller than half the wavelength of that radiation.
When it comes to optical microscopy, one way that scientists have overcome the diffraction limit is with a Nobel Prize-winning "super-resolution" technique known as photo-activated localization microscopy, which helps scientists image single molecules. First, researchers sprinkle an area with glowing molecules that blink on and off. These molecules are generally at least as far apart as the wavelengths of light they give off, so they can be distinguished from each other. Next, scientists image the area multiple times, letting just a few of the molecules glow each time. Superimposing these snapshots then yields an image composed of many blurry dots. The scientists know the glowing molecules are located at the centers of these dots of light, and by using computers to pinpoint these centers and sharpen these dots, the researchers can capture clear images of structures hundreds of times smaller than the wavelengths of the light they used to capture them.
Now, scientists in France have developed a similar technique based on ultrasound. They detailed their findings online in the 25 November edition of the journal Nature. They used their new method, which they call ultrafast ultrasound localization microscopy, to monitor the movements of clinically approved bubbles of inert gas 1 to 3 µm wide. They injected these microbubbles into the bloodstreams of live rats and imaged the single echoes that individual bubbles gave off when scanned with ultrasound pulses.
The French researchers imaged blood flow in rat brains at speeds of more than 500 frames per second, with pixel sizes less than 10 µm wide—about the width of a red blood cell—and more than 10 millimeters below the tissue surface. They suggest that their research might help pave the way toward deep, non-invasive ultrasound microscopy in animals and humans.