Healthy red blood cells are shaped a lot like lifesavers, just with more of a dimple than a hole in the middle. But red blood cells that are sick or damaged often change shape, becoming bloated when infected by the parasite that causes malaria, for example. Quickly detecting that irregular shape might one day speed up identification of blood diseases, certain kinds of cancer or even tell blood banks when red blood cells sitting in storage are past their prime—all without breaking the skin or spilling a single drop of blood.
A new imaging approach called photoacoustics may one day help that dream become a reality. The procedure, which harnesses the power of light and sound, is akin to laser-induced ultrasound. A team of investigators at Ryerson University in Toronto used high-frequency sound waves to create new, detailed images of red blood cells, bringing science one step closer to that future. The findings are published in Biophysical Journal today.
With photoacoustics, a drop of blood is placed under a special kind of microscope that picks up sounds produced by the cells themselves. Researchers then shoot a very focused laser beam at the samples. As the blood cells absorb energy from the laser pulse, they release some of it in another form—sound waves. Because blood’s composition allows it to absorb light in different ways at varying wavelengths scientists can work out various details about the shape of the cell using photoacoustics. “Think of it like a microphone,” says study author Michael Kolios, a physics professor at Ryerson and Canada Research Chair in biomedical applications of ultrasound. “We are just listening to what’s happening.”
The catch is that detecting changes in the shape of red blood cells at the level necessary to indicate the cells might be sick has not yet been possible via this kind of imaging.
Kolios and his colleagues at Ryerson tweaked a customized photoacoustic microscope to detect very high frequencies. Now they can recognize red blood cells’ shapes and sizes with greater definition than ever before. Their success opens the door for a future that could one day include handheld medical scanning devices that could map out cell shapes.
Previously, researchers could only use a frequency under 100 megahertz for their photoacoustic experiments because it is difficult to obtain sensors strong enough to work with larger frequencies. Images made from such low frequencies did not reveal much, allowing investigators to see that there was a cell there—but not much more. The Ryerson team was able to use much higher frequency sound waves thanks to a special ultrasound sensor that can pick up the higher frequencies. This improvement allowed them to “see” red blood cells in enough detail so that they could begin to tell how healthy the cell was.
They still had to look at red blood cells under a slide, however, because sound travels so unpredictably when it enters into bodily chasms. When a pregnant woman has an ultrasound, for example, medical professionals employ a very low frequency to get images of her fetus because a high-frequency wavelength would arrive at the fetus but then would quickly scatter and be absorbed by surrounding tissue before leaving the woman’s body. Similarly, using high frequencies in photoacoustics would not elicit a detailed image on something that exists in the body’s recesses.
While there are still a number of technical issues to work out, researchers are encouraged by the clarity of the images that are now available with photoacoustics. The next step, says Lihong Wang, a biomedical engineer at Washington University in Saint Louis, is to think about culling information from places where blood vessels are relatively accessible, like the arm. “This will inspire some new work, and we may start looking at photoacoustic information for the purpose of quantifying the shape of a single blood cell.” Wang says.
A more immediate application for photoacoustics may be scrutinizing blood in hospitals and blood banks that is about to be administered. Red blood cells have a shelf life of 42 days. “Unlike milk, where it’s really good one day and you pour it on your cereal the next and it’s sour, blood products start deteriorating right away—from zero to day 42,” says Jason Acker, who assesses new technology for Canadian Blood Services as its associate director of development. Although blood is assessed for contaminating bacteria, white blood cells and hemoglobin, the quality of the blood is never measured, he says, and it may deteriorate faster or slower depending on a variety of factors. “It could be valuable to have tools just prior to transfusion or prior to issuing blood to a hospital about the quality of the product.” Kolios has begun talks with Canadian Blood Services about partnering on research for adapting this technology to be used to help assess blood in blood banks.
Another long-term application of this work could be in detecting something like melanoma. “I’m most excited about the potential of this work for in vivo detection of circulating tumor cells,” because this technology could identify cancer cells more quickly than current methods, Wang says. To adapt this technology to do something like that, scientists would need to further calibrate the wavelengths they would use—red blood cells are red and most melanoma cells carry melanin, which is black, and thus would absorb light differently. But the possibilities from this breakthrough have scientists eyeing a brighter future for earlier and less invasive disease detection.