Data-Driven Information-Optimal Computational Microscopy

Optical microscopes have been an indispensable tool in biology and medicine for over three centuries. Unlike their simple predecessors, contemporary microscopes often employ complex robotic automation and customized algorithms. In the past decade, advances in high-performance computer processors, the ease of collecting massive datasets, and machine learning have created many new possibilities for data-driven approaches to microscope control and image analysis.This dissertation covers the challenges and opportunities in modern microscopy. First, it shows how neural networks can be used to create microscopes that adapt to the samples they are imaging in real time. For example, this paradigm can be used to quickly focus microscopes using inexpensive hardware or visualize developing immune responses at large scales. Next, new open-source software that facilitates development of these and other microscopy techniques is presented. Next, it turns to how microscopes can make measurements of the intrinsic optical properties of cells, from which their biological function can be inferred. Development of techniques that do so requires comparing approaches on standardized datasets, and the creation of such a dataset containing hundreds of thousands of images of single cells is described. Finally, a new theoretical framework for modeling the information transmission of both microscopes and image-processing algorithms is introduced. This perspective provides a new set of engineering principles for microscopes and opens a range of new research questions