Blockface histology with optical coherence tomography: A comparison with Nissl staining

Caroline Magnain, Jean C. Augustinack, Martin Reuter, Christian Wachinger, Matthew P. Frosch, Timothy Ragan, Taner Akkin, Van J. Wedeen, David A. Boas, Bruce Fischl

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Spectral domain optical coherence tomography (SD-OCT) is a high resolution imaging technique that generates excellent contrast based on intrinsic optical properties of the tissue, such as neurons and fibers. The SD-OCT data acquisition is performed directly on the tissue block, diminishing the need for cutting, mounting and staining. We utilized SD-OCT to visualize the laminar structure of the isocortex and compared cortical cytoarchitecture with the gold standard Nissl staining, both qualitatively and quantitatively. In histological processing, distortions routinely affect registration to the blockface image and prevent accurate 3D reconstruction of regions of tissue. We compared blockface registration to SD-OCT and Nissl, respectively, and found that SD-OCT-blockface registration was significantly more accurate than Nissl-blockface registration. Two independent observers manually labeled cortical laminae (e.g. III, IV and V) in SD-OCT images and Nissl stained sections. Our results show that OCT images exhibit sufficient contrast in the cortex to reliably differentiate the cortical layers. Furthermore, the modalities were compared with regard to cortical laminar organization and showed good agreement. Taken together, these SD-OCT results suggest that SD-OCT contains information comparable to standard histological stains such as Nissl in terms of distinguishing cortical layers and architectonic areas. Given these data, we propose that SD-OCT can be used to reliably generate 3D reconstructions of multiple cubic centimeters of cortex that can be used to accurately and semi-automatically perform standard histological analyses.

Original languageEnglish (US)
Pages (from-to)524-533
Number of pages10
StatePublished - Jan 1 2014

Bibliographical note

Funding Information:
Support for this research was provided in part by the National Center for Research Resources ( P41-RR14075 , U24 RR021382 ), the National Institute for Biomedical Imaging and Bioengineering ( R01EB006758 ), the National Institute on Aging ( AG022381 , 5R01AG008122-22 , K01AG028521 ), the National Center for Alternative Medicine ( RC1 AT005728-01 ), and the National Institute for Neurological Disorders and Stroke ( R01 NS052585-01 , 1R21NS072652-01 , 1R01NS070963 ), and was made possible by the resources provided by the Shared Instrumentation Grants 1S10RR023401 , 1S10RR019307 , and 1S10RR023043 . Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation , and by the NIH Blueprint for Neuroscience Research ( 5U01-MH093765 ), part of the multi-institutional Human Connectome Project.


  • Cytoarchitecture
  • Histology
  • OCT
  • Registration


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