3-D Histopathology with virtual slides

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<<< research with virtual slides

NEW >>> 3D images of tissue may help spot and treat cancer (BBC News) and Pubmed abstract (External sites - new pages)

N Roberts, D Magee, K Brabazon, M Shires, D Crellin, D Turner, Yi Song, P Quirke, D Treanor Pathology and Tumour Biology Group, Leeds Institute of Molecular Medicine, University of Leeds

3-D examination of tissue has significant potential to enhance the study of disease processes, particularly those involving structural or vascular changes in tissue.

Conventional histopathology in 3-D uses proven and simple laboratory techniques to study structure and function. However, computer processing and data visualisation constraints have limited the utility and scope of 3-D tissue reconstruction. Other limiting factors in 3-D histopathology include time consumption, accuracy, quality and levels of throughput.

We have developed a 3-D virtual microscope together with a custom image registration algorithm for virtual slides which:

  • Uses high performance computing with virtual slides, producing 3-D tissue reconstructions at a cellular resolution.
  • Uses data fusion techniques to allow visualisation of microanatomy and functional information in conjunction with the structural 3-D reconstruction.
  • Uses novel data visualisation techniques to allow researchers to explore the resulting datasets.
  • Uses an automated registration process of large amounts of tissue volumes at microscopic resolution to give a high throughput of 3-D reconstructions involving minimal user interaction.

The process involves serially sectioning hundreds of sections onto glass slides from a piece of paraffin embedded tissue:

paraffin block     water bath with sections

Then all these slides are stained and then scanned using Aperio software scanners creating virtual slides which are stacked and registered using specialised computer software:

aperio page

After registration these slices of liver with metastatic colorectal cancer can be viewed in the axial, coronal and sagittal planes. A large blood vessel near the tumour is highlighted in white:

tumour blood vessel

tumour blood vessel  tumour blood vessel

These stacks can then be visualised in 3-D which shows the carcinoma front in red and the blood vessels in the adjacent liver in yellow:

3-d of carcinoma

3-D reconstruction of whole sections is also possible, as demonstrated in this mouse embryo in which nearly 200 tissue sections were reconstructed to visualise the organs:

mouse embryomouse embryo

3-D reconstruction can also be used to visualise 3-D tissue models such as cirrhosis in the liver. This example shows Primary Biliary Cirrhosis (PBC) in the liver in which the cirrhotic nodules are stained pale yellow whilst the fibrotic scarring is stained red as a result of a Picro-Sirius red stain:

Picro-Sirius red stain

The model can be manipulated in the x, y and z axis in order for the pathologist to examine the cirrhosis in detail:

x, y and z axis manipulation

Because we are using high performance computing with virtual slides we can produce 3-D tissue reconstructions at a cellular resolution, such as this 3-D model of a single rat glomerulus:

single rat glomerulus 3-d model

The Bowman's capsule is reconstructed in 3-D (orange) with the proximal tubule exiting. The afferent (red) and efferent (yellow) arterioles can be seen exiting the capsule as well as the individual mesangial cells inside in green:

Bowman's capsule in 3-d

If you would like to know more or make use of our 3-D histopathology technologies please get in touch with Dr. Darren Treanor (darrentreanor@nhs.net)

<<< research with virtual slides

Department of Pathology and Tumour Biology,
Leeds Institute of Cancer and Pathology, University of Leeds. © 2016

University of Leeds   Leeds Institute of Cancer Studies and Pathology   NHS  

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