Imaging technologies have greatly advanced our understanding of biological systems. However, biological specimens are far from optimal structures for imaging as they are rife with optical inhomogeneities that seriously degrade image quality. Both excitation and emission light need to travel across the tissue to and from the focus point, and any deviation from the ideal path causes optical distortions. The result is that imaging biological specimens, even with high-end research microscopes, achieves far from ideal results, with images being increasingly degraded as one goes deeper into the tissue.

Adaptive optics can correct light distortions when imaging biological specimens. Credit: Marina Corral

Fortunately, astrophysicists have long encountered similar problems and devised ways to solve them. When imaging far-away galaxies using telescopes, light from remote stars enters the Earth's atmosphere, and atmospheric turbulence produces optical distortions that severely degrade the image. Telescopes can correct these distortions with adaptive optics, using a wavefront sensor that measures the distortions and a deformable mirror that is shaped to correct them.

So why can't these same principles be applied to improve the imaging of biological tissues? The application of adaptive optics in microscopy has lagged behind that in astronomy because of the difficulty in measuring the light's distortions in biological tissues (it is hardly possible to place a wavefront sensor within the specimen). Backscattered light from the sample can be used, but this method has only been successful when applied to relatively transparent samples such as the retina. To extend adaptive optics to many biological applications, especially in vivo tissue imaging, methods that enable measurement of the aberrations indirectly must be used.

One such method was recently described and applied to image cortical brain slices using two-photon microscopy (Nat. Methods 7, 141–147; 2010). By illuminating the sample through different light subapertures and measuring the relative displacements in each group of rays as they travel through the specimen toward the focus, enough information can be obtained to then correct these distortions and produce a nearly perfect image.

Although the application of adaptive optics to biological imaging has yet to be widely taken up, we expect to see further substantial efforts at marrying adaptive optics and microscopy to enable researchers to see more deeply and clearly into tissue