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Proceedings Paper

Zooming in: high resolution 3D reconstruction of differently stained histological whole slide images
Author(s): Johannes Lotz; Judith Berger; Benedikt Müller; Kai Breuhahn; Niels Grabe; Stefan Heldmann; André Homeyer; Bernd Lahrmann; Hendrik Laue; Janine Olesch; Michael Schwier; Oliver Sedlaczek; Arne Warth
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Paper Abstract

Much insight into metabolic interactions, tissue growth, and tissue organization can be gained by analyzing differently stained histological serial sections. One opportunity unavailable to classic histology is three-dimensional (3D) examination and computer aided analysis of tissue samples. In this case, registration is needed to reestablish spatial correspondence between adjacent slides that is lost during the sectioning process. Furthermore, the sectioning introduces various distortions like cuts, folding, tearing, and local deformations to the tissue, which need to be corrected in order to exploit the additional information arising from the analysis of neighboring slide images. In this paper we present a novel image registration based method for reconstructing a 3D tissue block implementing a zooming strategy around a user-defined point of interest. We efficiently align consecutive slides at increasingly fine resolution up to cell level. We use a two-step approach, where after a macroscopic, coarse alignment of the slides as preprocessing, a nonlinear, elastic registration is performed to correct local, non-uniform deformations. Being driven by the optimization of the normalized gradient field (NGF) distance measure, our method is suitable for differently stained and thus multi-modal slides. We applied our method to ultra thin serial sections (2 μm) of a human lung tumor. In total 170 slides, stained alternately with four different stains, have been registered. Thorough visual inspection of virtual cuts through the reconstructed block perpendicular to the cutting plane shows accurate alignment of vessels and other tissue structures. This observation is confirmed by a quantitative analysis. Using nonlinear image registration, our method is able to correct locally varying deformations in tissue structures and exceeds the limitations of globally linear transformations.

Paper Details

Date Published: 20 March 2014
PDF: 7 pages
Proc. SPIE 9041, Medical Imaging 2014: Digital Pathology, 904104 (20 March 2014); doi: 10.1117/12.2043381
Show Author Affiliations
Johannes Lotz, Fraunhofer MEVIS (Germany)
Judith Berger, Fraunhofer MEVIS (Germany)
Benedikt Müller, UniversitätsKlinikum Heidelberg (Germany)
Kai Breuhahn, UniversitätsKlinikum Heidelberg (Germany)
Niels Grabe, Ruprecht-Karls-Univ. Heidelberg (Germany)
Stefan Heldmann, Fraunhofer MEVIS (Germany)
André Homeyer, Fraunhofer MEVIS (Germany)
Bernd Lahrmann, UniversitätsKlinikum Heidelberg (Germany)
Ruprecht-Karls-Univ. Heidelberg (Germany)
Hendrik Laue, Fraunhofer MEVIS (Germany)
Janine Olesch, Fraunhofer MEVIS (Germany)
Michael Schwier, Fraunhofer MEVIS (Germany)
Oliver Sedlaczek, UniversitätsKlinikum Heidelberg (Germany)
Arne Warth, UniversitätsKlinikum Heidelberg (Germany)

Published in SPIE Proceedings Vol. 9041:
Medical Imaging 2014: Digital Pathology
Metin N. Gurcan; Anant Madabhushi, Editor(s)

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