High-resolution optical imaging techniques allowed the visualization of nanoscale biological structures and molecules. Current fluorescence-based super-resolution techniques are limited in throughput and quantification. We developed a high-resolution versatile imaging modality, called Vibrational Imaging of Swelled Tissues and Analysis (VISTA), based on a sample-expansion vibrational imaging strategy. We achieve label-free super-resolution imaging, and successfully used a U-net convolutional network to predict specific cellular features. We further applied VISTA to investigate protein aggregations in biological samples, including aggregates formed in Huntington’s disease and Alzheimer’s disease. This precise and multiplex high-resolution imaging modality opens new avenues for versatile biomedical studies.
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