MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice.

Large-scale cortical dynamics during natural behavior are difficult to measure because head-mounted imaging systems must balance field of view, spatial resolution, weight, and optical complexity. Existing wide-field miniature microscopes often rely on compound or custom-corrected optical assemblies, which increase device complexity and limit accessibility for laboratories without specialized optics expertise. Here, we present the Miniature Integrated Microlens Array System (MIMAS), an open-source head-mounted fluorescence microscope that replaces conventional multi-element optics with a 4 × 5 microlens array as its sole imaging element. By combining modular subfield acquisition with computational registration and stitching, MIMAS achieves cellular-resolution imaging across an approximately 4 × 4.5 mm2 field of view while weighing only 2.31 g. In freely behaving mice with sparse labeling of layer 2/3 cortical neurons, MIMAS enabled simultaneous calcium imaging across multiple dorsal cortical regions, with signals extracted from thousands of neurons. This broad sampling captured distributed cortical activity related to locomotor state and sparse position-modulated responses during open-field exploration without detectable disruption of locomotion or loss of signal quality over 30 min of recording. Beyond neuronal imaging, MIMAS also supported wide-field vascular imaging and resolved vessel caliber-dependent hemodynamic responses to isoflurane. These results establish MIMAS as a lightweight, accessible, and versatile platform for large-scale fluorescence imaging in freely behaving mice and demonstrate an alternative strategy for wide-field cortical imaging that lowers the optical complexity barrier for individual laboratories.