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Cortex-Wide, Cellular-Resolution Volumetric Imaging with a Modular Two-Photon Imaging Platform
Summary
This paper presents Meso2P, a new two-photon microscope capable of imaging the entire mouse cortex at single-cell resolution — a significant advance in neuroscience instrumentation. Among its demonstrated applications is the ability to track the distribution of micro- and nanoplastic particles in living brain tissue in real time. While primarily a neuroscience tool, its capacity to visualize nanoplastics in the brain non-invasively could become valuable for directly studying how plastic particles move through and accumulate in neural tissue.
Abstract Mapping cortex-wide neuronal activity at single-cell resolution has been limited by the physical tradeoff between numerical aperture and field-of-view (FOV) in two-photon microscopes. We present Meso2P, a modular two-photon platform that decouples excitation and detection by introducing a lateral paraboloid fluorescence collector. The design sustains an effective NA 0.87 over a contiguous 6 × 6 mm² FOV at high speed (2,048 × 2,048 pixels at 7.67 Hz). The modular platform can be upgraded with optional modules for simultaneous multi-plane imaging (1-4 planes at full resolution and speed), volumetric imaging (6 × 6 × 0.5 mm³, 2,048 × 2,048 × 28 voxels at 1 Hz capturing > 210,000 neurons), and holographic two-photon optogenetic stimulation for targeted perturbations. To handle the resulting large-scale data, we provide an open-source deep-learning pipeline that automates motion correction, segmentation, and spike inference. We demonstrate cortex-wide sensory responses, layer-specific network synchrony during anaesthesia, and in-vivo tracking of micro- and nanoplastic distribution. Meso2P therefore provides a reproducible route to high-throughput volumetric imaging across almost the entire cortex with high detection efficiency.
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