Sounding out the brain

Ultrasound isn’t just for images. Sonogenetics and other promising technologies let researchers use focused sound waves to control genes and entire cells deep in the tissues of living animals, without surgery.

Most parents’ first glimpse of their children comes in ultrasound images taken months before birth. But ultrasound could soon offer much more than prenatal portraits. In the past few years, researchers have opened a new door for ultrasound, developing techniques that harness the familiar, safe and noninvasive sound waves to control genes, alter brain function and deliver drugs to targets with millimeter precision.

The advance of what’s being termed sonogenetics offers a new twist on one of biology’s biggest recent successes. For about a decade, biologists have been able to control genes and nerve cells by activating light-sensitive proteins with laser light. The technique, known as optogenetics, has transformed the field of neuroscience, and its use is spreading to many other branches of biology. With light, researchers can now control the firing patterns of individual nerve cells, turn on specific regulatory genes in particular cells to see how this affects development, and do many other things. But optogenetics faces a critical shortcoming: Light doesn’t penetrate very far into living tissue, so its applications are mostly limited to tiny, transparent animals, cell cultures in petri dishes and where optical fibers can be surgically implanted into deeper tissue.

Ultrasound waves, in contrast, penetrate deep into tissues — hence their use for fetal imaging. They also can be focused almost as precisely as laser beams. At that millimeter-sized focus, ultrasound pulses can gently warm or physically jiggle cells. (More intense pulses can heat cells enough to kill them, an effect long used to destroy rogue regions of the brain to treat disorders such as essential tremor, a Parkinson’s-like disease.)

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