VCSELs Enable Deeper Brain Imaging

Using light to look more deeply into the living brain could give scientists a better understanding of how dementia, Alzheimer's disease and brain cancer develop over time.

Vertical-cavity surface-emitting lasers (VCSELs) are enabling a deeper look by increasing the sensitivity of swept-source optical coherence tomography (SS-OCT). Now, using a 1.3-μm VCSEL, researchers at the University of Washington have achieving an imaging depth of 2.3 mm in a live mouse with open-skull cranial window preparation. That's about twice as deep as in earlier OCT experiments.

The approach may enable examination of acute and chronic morphological or functional vascular changes in the deep brain, which has been rarely attempted before with OCT, the researchers said. A refined VCSEL swept-source OCT system could also enable full-length imaging of the human eye from cornea to retina, they said.

The work was published in the Journal of Biomedical Optics (doi: 10.1117/1.JBO.20.10.106004).

"The paper shows significantly enhanced imaging depth using a noninvasive laser-enabled technique for deep tissue imaging," said professor Martin Leahy of the National University of Ireland, Galway, a member of the journal's editorial board. "The authors demonstrate for the first time an application in which this capability opens up a whole new window into the live, intact hippocampus for discovery in brain research."

An optical coherence tomography image (a) visualizing morphological details of a mouse brain shows good correlation with photomicrograph (b) of a Nissl-stained histology section. Courtesy of Allen Institute for Brain Science.

OCT is used to obtain subsurface images of biological tissue at about the same resolution as a low-power microscope. An OCT camera can instantly deliver cross-section images of layers of tissue without invasive surgery or ionizing radiation.

Widely applied over the past two decades in clinical ophthalmology, it recently has been adapted for brain imaging in small animal models. Scientists have used OCT imaging to study the structure, neural activity and blood flow in the cerebral cortex of live mice.

Its application in neuroscience has been limited, however, because conventional OCT technology hasn't been able to image more than 1 mm below the surface of biological tissue.

OCT images are based on light directly reflected by subsurface tissues. At depths greater than 1 mm, ballistic photons that escape without scattering become too few to be detected, so conventional OCT systems have not been able to image deeper tissues such as the hippocampus, where many pathologies originate.