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4. Advanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments

Author

Savvidis, S, Ragazzini, R, de Rafael, V, Hutchinson, J, Massimi, L, Vittoria, F, Campinoti, S, Partridge, T, Ogunbiyi, O, Atzeni, A, Sebire, N, De Coppi, P, Mittone, A, Bravin, A, Bonfanti, P, Olivo, A, Savvidis, Savvas, Ragazzini, Roberta, de Rafael, Valeria Conde, Hutchinson, J. Ciaran, Massimi, Lorenzo, Vittoria, Fabio A., Campinoti, Sara, Partridge, Tom, Ogunbiyi, Olumide K., Atzeni, Alessia, Sebire, Neil J., De Coppi, Paolo, Mittone, Alberto, Bravin, Alberto, Bonfanti, Paola, Olivo, Alessandro, Savvidis, S, Ragazzini, R, de Rafael, V, Hutchinson, J, Massimi, L, Vittoria, F, Campinoti, S, Partridge, T, Ogunbiyi, O, Atzeni, A, Sebire, N, De Coppi, P, Mittone, A, Bravin, A, Bonfanti, P, Olivo, A, Savvidis, Savvas, Ragazzini, Roberta, de Rafael, Valeria Conde, Hutchinson, J. Ciaran, Massimi, Lorenzo, Vittoria, Fabio A., Campinoti, Sara, Partridge, Tom, Ogunbiyi, Olumide K., Atzeni, Alessia, Sebire, Neil J., De Coppi, Paolo, Mittone, Alberto, Bravin, Alberto, Bonfanti, Paola, and Olivo, Alessandro

Abstract

Background: The thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy has been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily for limited volumes. Methods: We used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on the microarchitecture of its structural components. We scanned 15 human thymi (9 foetal and 6 postnatal) with synchrotron radiation, and repeated scans using a conventional laboratory x-ray system. We used histology, immunofluorescence and flow cytometry to validate the x-ray findings. Results: Application to human thymi at pre- and post-natal stages allowed reliable tracking and quantification of the evolution of parameters such as size and distribution of Hassall's Bodies and medulla-to-cortex ratio, whose changes reflect adaptation of thymic activity. We show that Hassall's bodies can occupy 25% of the medulla volume, indicating they should be considered a third thymic compartment with possible implications on their role. Moreover, we demonstrate compatible results can be obtained with standard laboratory-based x-ray equipment, making this research tool accessible to a wider community. Conclusions: Our study allows overcoming the resolution and/or volumetric limitations of existing approaches for the study of thymic disfunction in congenital and acquired disorders affecting the adaptive immune system.

Published
2024

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Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Perosa, Valentina, Oltmer, Jan, Munting, Leon P., Freeze, Whitney M., Auger, Corinne A., Scherlek, Ashley A., van der Kouwe, Andre J., Iglesias, Juan E., Atzeni, Alessia, Bacskai, Brian J., Viswanathan, Anand, Frosch, Matthew P., Greenberg, Steven M., van Veluw, Susanne J., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Perosa, Valentina, Oltmer, Jan, Munting, Leon P., Freeze, Whitney M., Auger, Corinne A., Scherlek, Ashley A., van der Kouwe, Andre J., Iglesias, Juan E., Atzeni, Alessia, Bacskai, Brian J., Viswanathan, Anand, Frosch, Matthew P., Greenberg, Steven M., and van Veluw, Susanne J.

Published
2022

7. A next-generation, histological atlas of the human brain and its application to automated brain MRI segmentation.

Author

Casamitjana A, Mancini M, Robinson E, Peter L, Annunziata R, Althonayan J, Crampsie S, Blackburn E, Billot B, Atzeni A, Puonti O, Balbastre Y, Schmidt P, Hughes J, Augustinack JC, Edlow BL, Zöllei L, Thomas DL, Kliemann D, Bocchetta M, Strand C, Holton JL, Jaunmuktane Z, and Iglesias JE

Abstract

Magnetic resonance imaging (MRI) is the standard tool to image the human brain in vivo. In this domain, digital brain atlases are essential for subject-specific segmentation of anatomical regions of interest (ROIs) and spatial comparison of neuroanatomy from different subjects in a common coordinate frame. High-resolution, digital atlases derived from histology (e.g., Allen atlas [7], BigBrain [13], Julich [15]), are currently the state of the art and provide exquisite 3D cytoarchitectural maps, but lack probabilistic labels throughout the whole brain. Here we present NextBrain, a next-generation probabilistic atlas of human brain anatomy built from serial 3D histology and corresponding highly granular delineations of five whole brain hemispheres. We developed AI techniques to align and reconstruct ~10,000 histological sections into coherent 3D volumes with joint geometric constraints (no overlap or gaps between sections), as well as to semi-automatically trace the boundaries of 333 distinct anatomical ROIs on all these sections. Comprehensive delineation on multiple cases enabled us to build the first probabilistic histological atlas of the whole human brain. Further, we created a companion Bayesian tool for automated segmentation of the 333 ROIs in any in vivo or ex vivo brain MRI scan using the NextBrain atlas. We showcase two applications of the atlas: automated segmentation of ultra-high-resolution ex vivo MRI and volumetric analysis of Alzheimer's disease and healthy brain ageing based on ~4,000 publicly available in vivo MRI scans. We publicly release: the raw and aligned data (including an online visualisation tool); the probabilistic atlas; the segmentation tool; and ground truth delineations for a 100 μm isotropic ex vivo hemisphere (that we use for quantitative evaluation of our segmentation method in this paper). By enabling researchers worldwide to analyse brain MRI scans at a superior level of granularity without manual effort or highly specific neuroanatomical knowledge, NextBrain holds promise to increase the specificity of MRI findings and ultimately accelerate our quest to understand the human brain in health and disease., Competing Interests: Competing interests The authors have no relevant financial or non-financial interests to disclose.

Published
2024
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