CAREER: Deep-tissue optical imaging via inverse-scattering

An award is made to University of Texas at Austin to develop methods for deep-tissue optical imaging by computationally decoding light scattering in biological tissue. Optical imaging is popular for enabling high-resolution and high-speed bio-imaging with morphological and molecular contrast. However, it is limited by light scattering, which scrambles sample-specific information and restricts imaging depths to well below the distances that light can travel within tissue. Decoding this scrambled information could extend imaging depths by an order-of-magnitude, which would be transformative for large-scale 3D imaging of intact or in-vivo samples. Furthermore, project developments can be applied to any wave-based regime limited by scattering, such as acoustics, lidar, x-ray, etc. These developments will be closely integrated with the creation of the LegoCellScope platform, which will consist of modular and low-cost projects to train students on the theory and application of computational imaging. This resource will be shared through outreach programs and integrated into local school curricula, with the goal of equipping students with practical imaging skills that can support future careers in image science. This CAREER project will specifically focus on developing imaging pipelines to achieve computational scatter-correction in real-world biological samples. To accomplish this, project developments will develop: (1) novel hardware systems (both in transmission and reflection) that utilize specialized illumination modules to encode sample-specific scattering information into raw measurements; and (2) novel inverse-scattering frameworks (for diffracted and fluorescent light) combining physics-based models with data-driven approaches. Data-driven priors will be trained on ground-truth scattering measurements obtained from bio-mimicking physical and quasi-digital phantoms. This project aims to showcase these developments in the fields of developmental biology and neuroimaging by achieving extended imaging depths in scattering embryo and brain tissues. If successful, this would mark a major milestone toward overcoming the scattering limit, which is currently the primary challenge for deep-tissue imaging. 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.