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High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy


Stereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure’s segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.

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Color coding follows Grinberg and Heinsen (2007), Mesulam’s nomenclature is adapted from Mesulam et al. (1983)

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The authors would like to thank the team participating on the São Paulo-Würzburg collaborative project. This includes all members of the Brain Bank of the Brazilian Aging Brain Research Group (BBBABSG) of the University of São Paulo Medical School, Mrs. E. Broschk and Mrs. A. Bahrke from the Morphological Brain Research Unit of the University of Würzburg, Germany.

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Correspondence to Eduardo Joaquim Lopes Alho.

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This study was supported by resources from the University of Sao Paulo School of Medicine, Brazil and University of Würzburg, Germany. The author Eduardo Joaquim Lopes Alho was supported by a scholarship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) agency, Brazil, for doctoral studies at the University of Würzburg, Germany. The authors do not have personal financial or institutional interest in any of the drugs, materials, or devices described in this article.

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The authors disclose any actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.

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Alho, E.J.L., Alho, A.T.D.L., Grinberg, L. et al. High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy. Brain Struct Funct 223, 1121–1132 (2018).

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  • Cytoarchitecture
  • Thalamus
  • Sub-cortical atlas
  • Magnetic resonance imaging