Block-Centric Visualization Of Histological Whole Slide Images With Application To Revealing Growth-Patterns Of Early Colorectal Adenomas And Aberrant Crypt Foci
Comfortable navigation through diagnostic images is a prospective challenge for the acceptance of virtual microscopy applications in routine pathology ,. Tracing different regions of interest through multiple sections on one or several slides is a typical task in diagnostic slide examination. This laborious and time-consuming co-localization is currently executed by pathologists. Retaining the relative positions of tissue structures while alternating between multiple slides is still not feasible in a satisfactory manner in conventional nor virtual microscopy.
To address this issue we present a more comfortable and intuitive method to read slides using computer-assisted navigation. Furthermore, we demonstrate the strengths of our method by applying it to large series of serial colorectal tissue sections, creating new kinds of visualizations of different adenomatous mucosal architectures in human tissue, while looking for human correlates of lesions recently described in mice .
Histological images contain multiple distortions from different sources in the laboratory and digitalization process. An interconnection model was created to describe distortions by several layers, providing a normalized tissue representation. Layers were associated with specific distortions with each layer serving as a new level of abstraction. The first layers enabled a coarse alignment of tissue sections. Further alignment is achieved by piecewise, multi-resolution, SIFT-based  correspondence extraction and refinement. Inside the convex hull of all fiducial points local affine transformations were applied whereas a global affine transformation was used on the outside. Animated stacks were generated for regions of interest using local rigid transformations to preserve exact morphological coherences. For subsequent creation of 3D models, the relevant histological objects within these images were annotated by pathologists, partly using computer assisted segmentation based on active contours . These annotations were used subsequently to create simplified 3D models by applying VTK .
The presented methods provide an efficient means to retrieve correspondences and additional spatial information from serial sections of histological slides. They also show good applicability for specimen from different origin. Alignment methods can be applied to generate block-centric visualizations such as parallel and transparent viewing of multiple stains. Moreover, the generated stack videos and 3D models demonstrate the very good accuracy of section alignment even in large series. The visualizations enable pathologists and researchers to grasp the 3D structural relationships in the tissue at a glance, providing an excellent tool to communicate more complex histomorphological findings. Interestingly, we see two kinds of tubular adenomas, which could imply multiple ways to tubular adenoma formation in FAP-patients, possibly akin to the recent observations in mice .
2009, 40(8): 1057-69.
 LeÅ¡kovskÃ½ P., et. al., Point based registration of high-resolution histological slices for navigation purposes in virtual microscopy, Annals
of the BMVA 2012, 10:1-18.
 Schwitalla S., et al., Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties, Cell. 2013,
152(1-2):25 â€“ 38.
 Lowe D.G., Distinctive Image Features from Scale-Invariant Keypoints, International Journal of Computer Vision 2004, 60(2): 91-110.
 Xu C., et.al., Medical Image Segmentation Using Deformable Models, SPIE Handbook on Medical Imaging - Volume III, Medical Image
Analysis, SPIE Press 2000.
 Schroeder W., et.al., The Visualization Toolkit, 2004. ISBN: 1930934122 Available from: http://www.vtk.org/
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
4. In case of virtual slide publication the authors agree to copy the article in a structural modified version to the journal's VS archive.