Imaging the small with the small: Prospects for photonics in micro-endomicroscopy for minimally invasive cellular-resolution bioimaging

Many bioimaging studies, including those in engineered tissue constructs, intravital microscopy in animal models, and medical imaging in humans, require cellular-resolution imaging of structures deep within a sample. Yet, many of the current approaches are limited in terms of resolution, but also in invasiveness, repeatable imaging of the same location, and accessible imaging depth. We coin the term micro-endomicroscope to describe the emerging class of small, cellular-resolution endoscopic imaging systems designed to image cells in situ while minimizing perturbation of the sample. In this Perspective, we motivate the need for further development of micro-endomicroscopes, highlighting applications that would greatly benefit, reviewing progress, and considering how photonics might contribute. We identify areas ripe for technological development, such as micro-scanners and small lens systems, that would advance micro-endomicroscope performance. With the right developments in photonics, many possibilities exist for new minimally invasive translatable imaging tools across the scientific, pre-clinical, and clinical spectrum: from longitudinal studies of engineered tissue constructs, to tracking disease progression in animal models, to expanding the ability to diagnose and develop treatments for diseases without the need for invasive medical procedures