001     1048785
005     20251204202145.0
037 _ _ |a FZJ-2025-04900
041 _ _ |a English
100 1 _ |a Huysegoms, Marcel
|0 P:(DE-Juel1)138708
|b 0
|e Corresponding author
|u fzj
111 2 _ |a 9th BigBrain Workshop - HIBALL Closing Symposium
|c Berlin
|d 2025-10-27 - 2025-10-29
|w Germany
245 _ _ |a Towards a Cellular 3D Model of the Human Brain at 1µm Isotropic Resolution
260 _ _ |c 2025
336 7 _ |a Conference Paper
|0 33
|2 EndNote
336 7 _ |a INPROCEEDINGS
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|s 1764842346_5626
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|x After Call
520 _ _ |a Background: 3D histological reconstruction is well established at mesoscopic scales (~20µm). At this resolution, the task can be framed as an optimization of spatial transformations driven by pixel-level similarity metrics, typically within coarse-to-fine reconstruction frameworks that integrate both slice-to-slice and histology-to-reference registrations (Amunts et al., 2013; Alkemade et al., 2022).
We aimed to address these challenges through the development of a novel framework for 3D reconstruction of histological sections that accurately represents the original volume using a three-step feature-matching and global optimization strategy.

Methods: Optical z-scanning enables imaging of twenty depths within each 20 µm thick histological section by gradually shifting the focal plane, resulting in a 1 µm isotropic resolution volume per section. The principal challenge then lies in accurately reconstructing the sections to achieve a faithful representation of the anatomy of the unsliced brain. Our approach involves (i) computing point correspondences between neighbouring sections (e.g. bisected cells or blood vessels). Then, (ii) optimize a global cost function to jointly estimate the spatial coordinates of matched features across all sections, enforcing both matching and smoothness constraints. Finally, (iii) to produce the final volume, polyaffine transformations are fitted to warp each histological section onto the optimized feature positions.

Results: We compared our global reconstruction approach against several other strategies, demonstrating its potential to outperform standard sequential pipelines in terms of alignment accuracy, structural smoothness, and anatomical preservation. The final reconstructed volume maintains natural cortical curvature, resolves laminar organization throughout the cortex (even in oblique cutting planes) and preserves overall brain shape.

Conclusion: Our framework provides a robust, scalable foundation for building cellular-resolution 3D models of the human brain. It makes minimal assumptions about feature types, accommodating both traditional descriptors (e.g., SURF) and ML-based detectors (e.g., LightGlue). The method also generalizes across different tissue stainings and section thicknesses (10–60 µm). Although the approach can operate without a reference volume, one can be incorporated to better preserve overall shape in cases of substantial nonlinear tissue deformation. Future work will generate detailed, region-specific descriptions of cellular organization, which can in turn support realistic simulations of human brain activity.
536 _ _ |a 5254 - Neuroscientific Data Analytics and AI (POF4-525)
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536 _ _ |a 5251 - Multilevel Brain Organization and Variability (POF4-525)
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536 _ _ |a HIBALL - Helmholtz International BigBrain Analytics and Learning Laboratory (HIBALL) (InterLabs-0015)
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536 _ _ |a EBRAINS 2.0 - EBRAINS 2.0: A Research Infrastructure to Advance Neuroscience and Brain Health (101147319)
|0 G:(EU-Grant)101147319
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|f HORIZON-INFRA-2022-SERV-B-01
|x 3
536 _ _ |a Helmholtz AI - Helmholtz Artificial Intelligence Coordination Unit – Local Unit FZJ (E.40401.62)
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700 1 _ |a Kropp, Jan-Oliver
|0 P:(DE-Juel1)171152
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700 1 _ |a Wenzel, Susanne
|0 P:(DE-Juel1)174282
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700 1 _ |a Oliveira, Sarah
|0 P:(DE-Juel1)7935
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700 1 _ |a Paquola, Casey
|0 P:(DE-Juel1)187055
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700 1 _ |a Amunts, Katrin
|0 P:(DE-Juel1)131631
|b 5
|u fzj
700 1 _ |a Dickscheid, Timo
|0 P:(DE-Juel1)165746
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856 4 _ |u https://events.hifis.net/event/2171/contributions/20178/
909 C O |o oai:juser.fz-juelich.de:1048785
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|v Decoding Brain Organization and Dysfunction
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