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CleLight: A scalable 3D histology pipeline for mappingneurodegenerative and psychiatric pathology in archivalhuman brains

Jorda-Siquier, T.; Scholler, J.; Gantar, I.; Policet-Betend, H.; Batti, L.; Pages, S.; Kovari, E.; Lamy, C. M.

2025-12-13 neuroscience
10.64898/2025.12.10.693496 bioRxiv
Show abstract

Mesoscopic brain imaging, enabled by advances in tissue clearing, light-sheet microscopy, and large-scale image processing, allows detailed analysis of cellular and molecular architecture across whole neural circuits. However, applying these methods to postmortem human brain tissue is hindered by strong autofluorescence, high tissue density, and fixation-induced damage. We introduce CleLight, a light-enhanced clearing method that increases tissue transparency while quenching autofluorescence. Combined with complementary chemical treatments, CleLight supports multiplexed immunolabeling and high-resolution imaging of centimeter-thick, formalin-fixed, paraffin-embedded human brain sections. It is compatible with a wide range of antibodies and fluorescent dyes, enabling the visualization of physiological and pathological features across diverse CNS regions in healthy and diseased samples. CleLight offers a simple, robust, and scalable workflow for clearing, deep labeling, and volumetric imaging of human brain tissue. Its compatibility with conventional histology and archival material makes it well suited for organ-wide pathological studies in large patient cohorts and historical brain collections.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.