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bioRxiv · 10.64898/2026.06.28.735089

Genetically Encoded Melanin as a Photostable Scattering Contrast for Whole-Brain Tomography

Gu, P.·Chen, C.·Ren, J.
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Abstract

Large-scale brain imaging has traditionally depended on fluorescent reporters, but challenges like photobleaching and inconsistent signals hinder quantitative analysis in intact tissues. In response, we present MelaCAST (melanin-based scattering CAST imaging), a novel genetically encoded scattering method for whole-brain visualization. Using AAV to deliver tyrosinase allows for cell-type-specific melanin synthesis, providing a stable intracellular scattering contrast across the mouse brain. Combining tissue clearing with scattering tomography, MelaCAST offers non-photobleaching, high-throughput volumetric imaging of genetically targeted cell populations in intact brains. This technique establishes melanin as a genetically encoded scattering reporter and broadens whole-organ imaging capabilities beyond traditional fluorescence methods.

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Gu, P., Chen, C., Ren, J.. 2026-07-02. Genetically Encoded Melanin as a Photostable Scattering Contrast for Whole-Brain Tomography. https://doi.org/10.64898/2026.06.28.735089

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