Ultrasound Goes Microscopic to Image Living Organs

A new imaging technique using ultrasound and microscopic bubbles has allowed researchers to peer deep into living organs. The ultrafast microscopy method being pioneered by a research team in Paris can produce images at the rate of more than 500 frames a second. They used it to non-invasively view blood flowing through microscopic vessels in a complete living rat brain, as shown in the image above.

“We anticipate that ultrafast ultrasound localization microscopy may become an invaluable tool for the fundamental understanding and diagnostics of various disease processes that modify the microvascular blood flow, such as cancer, stroke and arteriosclerosis,” Langevin Institute physicist Mickael Tanter and colleagues conclude in a study published last week in the journal Nature.

Their work could represent a breakthrough in using ultrasound for imaging, which is limited to resolving objects at the millimeter-scale in conventional approaches. At the heart of the problem they cracked is something called the diffraction limit, a fundamental barrier in which objects can’t be resolved if they are smaller than about half the wavelength of the radiation being used to view them.

The group figured out a workaround by injecting bubbles as small as 1 micron in diameter into the animal’s bloodstream. These microbubbles acted as acoustic targets for ultrasound waves to scatter and bounce off. This allowed Tanter and colleagues to conduct super-resolution imaging of microvessels in the brain with a pixel resolution about the size of red blood cells, a tenfold improvement over current methods.

Ultrafast ultrasound localization microscopy, “by removing the diffraction-induced trade-off between resolution and penetration of ultrasound waves, emerges as the first in vivo technique for imaging and quantifying blood flow at microscopic resolution deep into living organs,” the group writes.



Ben Cox and Paul Beard, experts in acoustics at the University College of London who did not take part in the research, said there are still a number of problems to overcome before the advance can be translated to medical use. Before it can be used on a human brain, they say, researchers will need to figure out how to get ultrasound wavelengths through the thick human skull, which naturally attenuates this type of radiation. And the need to introduce microbubbles into the bloodstream could also significantly increase the time it would take to perform scans.



Still, they write in a commentary accompanying the study, “Super-resolution ultrasound imaging of microvasculature is an exciting prospect. The technique has the potential to substantially advance the study of normal blood-vessel function, as well as disease. Moreover, it might enable doctors to readily identify microvessel-related disorders, such as tumor-related vessel growth and microvascular abnormalities in deep abdominal organs such as the kidneys, and to assess cardiovascular disease.”

Top Image: Image of the whole brain vasculature at microscopic resolution in the live rat using ultrafast Ultrasound Localization Microscopy: Local density of intravascular microbubbles in the right hemisphere, quantitative estimation of blood flow speed in the left hemisphere. Photo and caption courtesy of ESPCI/INSERM/CNRS.