The high spatiotemporal resolution brain imager enables voltage-sensitive fluorescence imaging of neuronal action potentials with sub-micron spatial and sub-millisecond temporal details. This technology uses an innovative active-sensing approach and two complementary detection channels to achieve high spatiotemporal resolution neural imaging with high signal to noise ratio, but without saving an overwhelmingly large amount of data by only recording a number of regions of interest (ROIs) that have neuronal activities. The device is compatible with various imaging platforms including standard microscopes and animal head-mounted imagers. A broad range of excitation/emission wavelengths are available upon customer request.