Compressive streak microscopy for fast sampling of fluorescent reporters of neural activity.

SIGNIFICANCE: In vivo one-photon fluorescence imaging of calcium and voltage indicators expressed in neurons enables noninvasive recordings of neural activity with submillisecond precision. However, data acquisition speed is limited by the frame rate of cameras. AIM: We developed a compressive streak fluorescence microscope to record fluorescence in individual neurons at high speeds (  ≥ 200 frames per second) exceeding the nominal frame rate of the camera by trading off spatial pixels for temporal resolution. APPROACH: Our microscope leverages a digital micromirror device for targeted illumination, a galvo mirror for temporal scanning, and a ridge regression algorithm for fast computational reconstruction of fluorescence traces with high temporal resolution. RESULTS: In simulations, the ridge regression algorithm reconstructs traces of high temporal resolution with limited signal loss. Validation experiments with fluorescent beads and experiments in larval zebrafish demonstrate accurate reconstruction with a data compression ratio of 10 and accurate recordings of neural activity with 200- to 400-Hz sampling speeds. CONCLUSIONS: Our compressive microscopy enables new experimental capabilities to monitor activity at a sampling speed that outpaces the nominal frame rate of the camera.