We present a computational approach for hyperspectral computational Selective Plane Illumination Microscopy (SPIM), offering fast 3D imaging with reduced photobleaching. Inspired by Hadamard spectroscopy, our method employs structured light sheets via a digital micromirror device. A data-driven reconstruction strategy, implemented through an end-to-end trained neural network, demonstrates robust performance under varying noise levels. Leveraging non-negative least squares minimization, we obtain component maps, exemplifying applications such as autofluorescence removal in transgenic zebrafish and discrimination of closely matched red proteins. Our findings showcase the potential of computational strategies to advance hyperspectral SPIM in photonic research.
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