CAREER: Hybrid adaptive optics: a new paradigm for faster, deeper, volumetric microscopy in scattering media

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Optical microscopy has played a key role in biomedical discoveries for clinical management of disease, but significant challenges remain for applications that require rapid, non-invasive imaging over large volumes, particularly when imaging deep into optically dense biological media. This proposal addresses these limitations by developing new ways of splitting up, and sharing the work of image formation between state-of-the-art computational and hardware approaches. These methods will be demonstrated by imaging biological phenomena that cannot be studied with existing methods. The accompanying education and outreach activities will foster a broader appreciation for biomedical optics and imaging, and train scientists and engineers to effectively interact with, and engage the public. Outreach aspects of this proposal will create experiential and interactive inquiry-based workshops for middle and high school students, develop interactive demonstrations for the Ithaca Sciencenter and train graduate students to effectively communicate their science with the public. High-throughput volumetric microscopy deep in biological media is important for the study of dynamic biological processes, such as the biophysical interactions associated with collective cell migration, or neural network activity in the mouse brain. Optical coherence microscopy (OCM) and three-photon microscopy (3PM) are currently the modalities that enable the deepest microscopic imaging in scattering biological samples. However, their volumetric imaging speed and penetration depth is currently limited by depth-dependent photon collection, or by wavefront distortions due to aberrations and multiple scattering. This proposal will synergistically combine hardware adaptive optics (AO) and computational adaptive optics (CAO), to dramatically improve the speed and imaging depth range of volumetric OCM and 3PM.This hybrid AO approach will be used to launch new avenues of investigation, including studies on inter-cell coordination of cell traction forces during 3D migration, and investigations on the connection between behavior and spatiotemporal patterns of neural network activity deep in the mouse brain.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.