Deep tissue imaging with nonlinear optical microscopy: Current Opportunities & Challenges for Adaptive Optical Techniques

Special Solid State & Optics Seminar Series

Alexander Jesacher

Institute of Biomedical Physics, Medical University of Innsbruck, Austria

Light microscopy provides an arsenal of techniques for investigating the behavior of life at microscopic length scales. While optical microscopes provide excellent image quality at the surface of a glass coverslip, their performance inevitably degrades as one attempts to image deeper into heterogeneous cellular networks and tissues. However, imaging deep into tissues is often required to understand disease development and the interaction of different cell types. 

Non-linear microscopy techniques, such as two-photon excitation fluorescence (TPEF) microscopy, are excellent tools for imaging deep tissue. However, even their imaging depth is limited by wavefront distortion caused by the specimen. 

Adaptive optics (AO) is a technology that counteracts these aberrations to restore diffraction-limited imaging performance. Originally developed for astronomical imaging, AO combines wavefront sensing with physical correction of aberrations using a spatial light modulator. 

Recently, AO research has been exploring the regime of strong turbulence compensation, where photons are multiply scattered. This regime has the potential to provide entirely new insights, but also presents new challenges in terms of the speed of wavefront measurement and the size of the ‘window’ through which a clear view of the sample can be obtained. 

In my talk I will review the current state of the art of AO for nonlinear microscopy & highlight recent developments towards seeing through such strongly scattering media. 

I will present one of our recent developments, a fast indirect wavefront sensing strategy for nonlinear imaging based on joint amplitude and phase shaping. I will also present our ideas for increasing the size of the corrected field of view, which is one of the biggest hurdles to overcome in scatter compensation.

Sponsored by:
The Flint Fund Series on Quantum Devices & Nanostructures