Human brain as the center of the nervous system controls our physiology, consciousness, and behavior. The function of the brain relies on the interactions of tens of billions of neurons through tens of trillions of synapses. Gaining precise knowledge of neural circuits relies on innovative and transformative tools for quantitative measurement of cellular dynamics and signaling in the live brain. Our lab works at the interface of optical engineering, device fabrication, image processing, and neuroscience to deliver enabling tools for neuroscience research. Specifically, we are working on three frontiers. First, the major challenge of cellular resolution function recording is the superficial access depth. Current methods are limited to ~ 1 mm depth, insufficient to access deep brain regions. We have developed Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for deep-brain large-scale neurophotonic interface. I will present the results of applying COMPACT for deep-brain calcium imaging. Second, high-performance glutamate sensors and voltage indicators are on the horizon. Seeing information flow at millisecond time scale with subcellular resolution among neural circuits in the live mammalian brain is about to become a reality. However, currently available imaging tools are insufficient to keep up with the sensor response. We have developed an optical gearbox that can convert existing scopes for such high-speed measurement. I will present the results of in vivo kHz imaging. Third, cellular resolution recording has been limited to animal models. In comparison, fMRI and ultrasound can be applied to human brain. Can we leverage the advance of cellular resolution recording to address the key challenges of human brain measurement modalities? I will discuss the latest progress on the multimodal imaging of mammalian brain.