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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.10.612232
preprint
1
Article
Quantitative cytoarchitectural phenotyping of deparaffinized human brain tissues
Meo Danila Di
Sorelli Michele
Ramazzotti Josephine
Cheli Franco
Bradley Samuel
Perego Laura
Lorenzon Beatrice
Mazzamuto Giacomo
Emmi Aron
Porzionato Andrea
Caro Raffaele De
Garbelli Rita
Biancheri Dalila
Pelorosso Cristiana
Conti Valerio
Guerrini Renzo
Pavone Francesco S.
Costantini Irene http://orcid.org/0000-0002-8464-7324

14 9 2024
2024.09.10.612232https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.09.10.612232
nihpp-2024.09.10.612232.pdf
Abstract

Advanced 3D imaging techniques and image segmentation and classification methods can profoundly transform biomedical research by offering deep insights into the cytoarchitecture of the human brain in relation to pathological conditions. Here, we propose a comprehensive pipeline for performing 3D imaging and automated quantitative cellular phenotyping on Formalin-Fixed Paraffin-Embedded (FFPE) human brain specimens, a valuable yet underutilized resource. We exploited the versatility of our method by applying it to different human specimens from both adult and pediatric, normal and abnormal brain regions. Quantitative data on neuronal volume, ellipticity, local density, and spatial clustering level were obtained from a machine learning-based analysis of the 3D cytoarchitectural organization of cells identified by different molecular markers in two subjects with malformations of cortical development (MCD). This approach will grant access to a wide range of physiological and pathological paraffin-embedded clinical specimens, allowing for volumetric imaging and quantitative analysis of human brain samples at cellular resolution. Possible genotype-phenotype correlations can be unveiled, providing new insights into the pathogenesis of various brain diseases and enlarging treatment opportunities.
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pmc
