“Twinkle twinkle little blood cell”

A technique pioneered in astronomy is helping scientists to track single blood cells as they move across the back of the eye.

Adaptive optics is helping to track the speed of individual red blood cells moving across the back of the eye. Faster cells are shown in red, slower cells in blue. Image credit: Jesse Schallek, Keith Parkins and Aby Joseph (CC BY 4.0)

The magical twinkling of the night sky is actually the result of imperfections in Earth's atmosphere. Turbulence in the air distorts the light as it passes through, causing it to bend, which blurs the image. To get a clear picture of distant objects, astronomers use a technique called 'adaptive optics'. Deformable mirrors, controlled by computers, bend the light back to correct the distortion. Now, biologists are borrowing the same technique to take a closer look at the blood vessels of the brain.

At the moment, functional MRI is one of the most popular imaging techniques for measuring blood flow in the brain. But it can only achieve a resolution of around 1 millimetre, and the tiniest capillaries measure less than a hundredth of a millimetre across. These tiny vessels can be examined surgically, or by injecting dyes into the bloodstream, but these techniques carry a risk. As a result, scientists can only use them in experimental animals.

One solution is to look at the vessel network in the back of the eye. The retina is part of the brain and, because the eye is transparent, its blood supply is much easier to see. But imperfections in the eye bend light and blur images of the cells, just like the Earth's atmosphere blurs images of the stars. This is where adaptive optics comes in. Using this technique, it becomes possible to see single red blood cells. Combining adaptive optics with high-speed video could allow us to track cells through the whole network of blood vessels in the eye. At the moment, blood flow measurement techniques either focus on the very big vessels, or the very small ones; they cannot get a complete picture of the whole interconnected system.

Now, Joseph et al. have combined adaptive optics, ultrafast imaging, and a new algorithm to view the whole blood vessel network in the eye of a mouse. The new method can automatically measure single blood cells, even when they are moving at their highest possible speed. It can capture the full range of retinal vessels, from the smallest capillaries to the largest arteries and veins. And, by tracking millions of cells at a time, it can reveal how the pressure wave of the blood changes with each beat of the heart.

The slightest disruption in blood flow to the brain can cause irreversible damage. So, measuring blood flow is crucial to understanding what happens when things go wrong. This new method is not invasive and uses safe levels of near-infrared light which the retina cannot see, making it safe to use in humans. Joseph et al. have already started their first studies in humans, and the baseline data they have obtained for healthy mice also provides a starting point for comparison with mice with genetic mutations or disease.