One percent of infants in the United States are born with cardiovascular abnormalities. The developmental processes that lead to these congenital problems aren’t visible in ultrasound scans, and the lack of tools for imaging mammalian development non-invasively at high resolution has hindered researchers’ attempts to understand these processes.
In the hopes of providing insights into how these developmental problems might be prevented, researchers at the University of Houston have developed an imaging system they’re using to take 3D video of the mammalian heart as it forms. In the video below, showing a mouse embryo that’s 8.5 days past conception, a normal heartbeat is visible. The mouse heart begins to form at 7.5 days.
The video was made using an imaging technology called optical-coherence tomography. Though it looks grainy, this and other video of the developing heart made by the Houston group are some of the best ever taken. “These are the first images at high resolution of the beating [mammalian] heart,” says Kirill Larin, assistant professor of biomedical and mechanical engineering at the University of Houston. “You can see the blood vessels, the heart chambers.” The current resolution of the technique is six micrometers and Larin expects to get it down to two.
Microscopy techniques can get much higher resolution, but they’re invasive. Ultrasound can go deeply enough into the body to image human embryos, but it’s low resolution. The Texas researchers developed a variation on optical coherence tomography that combines some of the advantages of each: it’s higher resolution than ultrasound, it’s noninvasive, and it can look deeper into the body than microscopy (not deep enough to work in people, but deep enough to watch a mouse embryo in the lab). Other studies of the developing heart have been done in fish and amphibians: they’re easier to see because these animals
are smaller. But their cardiovascular systems are significantly
different from our own. Many congenital cardiovascular problems result from the malformation of chambers of the heart. Fish hearts have just two chambers; amphibian hearts have three. Mammals such as mice and humans have a four-chambered heart, and using the Houston technique, Larin can watch those chambers form.
Optical coherence tomography works on a similar principle to ultrasound. A beam of laser light is sent through the embryo, and when it bounces back it’s combined with an interfering reference beam. By examining the effect of the light on the reference beam, it’s possible to determine how far it traveled and this information is reconstructed to form an image. The Houston group didn’t invent the technique, which is commonly used for clinical imaging of the retina. They adapted existing hardware and software to make them suitable for imaging embryos.
Larin, who presented the imaging technology last week at the Frontiers in Optics Conference in San Jose, CA, says his group is now studying mouse embryos with developmental disorders.
This image of a mouse embryo was made 8.5 days after conception and shows some of the structures visible in the video. The pericardial sac is the structure surrounding the heart; the ventricle is one of the heart’s chambers; the outflow tract is the structure from which blood will flow into the arteries and then on to the rest of the body.
Credit: Kirill Larin