A large-angle optical raster scanning system for high-speed deep tissue imaging, being provided with field of view, hereinafter called FOV, of at least one square millimeter with sub-femtoliter effective 3D resolution resolved by Nyquist-exceeded synchronized sampling, comprising: one or more, i.e., 1st to nth, pulsed laser source(s) for emitting one or more laser beams with central wavelengths of λ n and a Nyquist-exceeding repetition rate of R n ≥ A n × N n for the nth pulsed laser source, where A n is a Nyquist-limited sampling rate given by 4 times the horizontal FOV multiplied by a resonant scanner frequency divided by theoretical objective-limited lateral resolution, for resolving micro-optical resolution across a horizontal FOV of >1 mm, and N n is an integer ≥ 1 signifying a number of laser pulse(s) per voxel; a resonant scanning mirror optically coupled to the one or more pulsed laser source(s); a galvanometer scanning mirror optically coupled to the resonant scanning mirror; a scan lens optically coupled to the galvanometer scanning mirror; a dedicated tube lens, comprising three plano-convex lenses, each with an effective focal length of 500 mm, combined together and optically coupled to the scan lens; a high-numerical aperture, hereinafter called high-NA, and low magnification objective lens optically coupled to the dedicated tube lens for raster scanning a volumetric tissue-sample and for collecting a sample-generated fluorescence signal which is guided to a photomultiplier tube, PMT, to produce an electrical signal; and a data acquisition system coupled to receive the electrical signal from the PMT with each sampling event synchronized to each optical pulse either from the one pulsed laser source, or from the highest repetition rate pulsed laser source, in case of one, or more pulsed laser source(s), respectively, wherein the scan lens and the dedicated tube lens constitute a beam expander with low magnification, thereby maximizing the FOV, but concurrently providing an enlarged beam size over a back aperture of the high-NA and low magnification objective lens to maintain high excitation-NA, and thereby high-resolution. one or more, i.e., 1st to nth, pulsed laser source(s) for emitting one or more laser beams with central wavelengths of λ n and a Nyquist-exceeding repetition rate of R n ≥ A n × N n for the nth pulsed laser source, where A n is a Nyquist-limited sampling rate given by 4 times the horizontal FOV multiplied by a resonant scanner frequency divided by theoretical objective-limited lateral resolution, for resolving micro-optical resolution across a horizontal FOV of >1 mm, and N n is an integer ≥ 1 signifying a number of laser pulse(s) per voxel; a resonant scanning mirror optically coupled to the one or more pulsed laser source(s); a galvanometer scanning mirror optically coupled to the resonant scanning mirror; a scan lens optically coupled to the galvanometer scanning mirror; a dedicated tube lens, comprising three plano-convex lenses, each with an effective focal length of 500 mm, combined together and optically coupled to the scan lens; a high-numerical aperture, hereinafter called high-NA, and low magnification objective lens optically coupled to the dedicated tube lens for raster scanning a volumetric tissue-sample and for collecting a sample-generated fluorescence signal which is guided to a photomultiplier tube, PMT, to produce an electrical signal; and a data acquisition system coupled to receive the electrical signal from the PMT with each sampling event synchronized to each optical pulse either from the one pulsed laser source, or from the highest repetition rate pulsed laser source, in case of one, or more pulsed laser source(s), respectively, wherein the scan lens and the dedicated tube lens constitute a beam expander with low magnification, thereby maximizing the FOV, but concurrently providing an enlarged beam size over a back aperture of the high-NA and low magnification objective lens to maintain high excitation-NA, and thereby high-resolution.