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Why every hospital should have a micro-CT: 3D x-ray histology, let’s go beyond standard 2D histology

Why every hospital should have a micro-CT: 3D x-ray histology, let’s go beyond standard 2D histology
Why every hospital should have a micro-CT: 3D x-ray histology, let’s go beyond standard 2D histology
Living structures are an intricate threedimensional (3D) arrangement of cells and tissue matrix across many length scales. Contemporary capabilities to quantify tissue architecture, connectivity and cell relationships are however fundamentally constrained by a lack of 3D analytical platforms with appropriate resolution, penetration, structural differentiation, consistency, volumetric analysis capability and sample throughput. Structural analysis of tissues, whether for research or diagnostic purposes, remains overwhelmingly bounded and constrained by microscopic examination of relatively sparse 2D tissue sections, providing only a snapshot from which 3D spatial relationships can only be inferred. Therefore, whilst 3D medical imaging is commonplace, microscopic tissue structure analysis (i.e., histology) remains overwhelmingly wedded to 200-year-old practices of microscopic 2D examination of tissue sections. We have demonstrated previously that Xray imaging by micro-computed tomography (μCT) allows non-invasive 3D imaging of the microstructure of standard tissue biopsies 1. This yields details comparable to twodimensional (2D) optical microscope sections but for the whole tissue volume, which can for example overturn misconceptions of disease development based on 2D assessment. One exemplar is the pathogenesis of idiopathic pulmonary fibrosis 2, where 3D structural insight into co-localisation of tissue features and dysmorphia within substantive tissue volumes suggested previously unrecognised fibroblast foci plasticity. Based on this encouraging μCT results for soft tissues, in collaboration with an industrial partner, we developed a customdesign and soft-tissue optimised μCT scanner (Wellcome Trust Pathfinder Award, 2016- 17). Currently, we are establishing the foundations for routine 3D X-ray histology (Wellcome Trust Biomedical Resource and Technology Development, 2019-2022), including new X-ray equipment and standardised & automated workflows, where sample throughput will be increased and scan times reduced, providing the foundations for day-to-day 3D X-ray histology. Applicable to vast existing sample archives and a wide range of soft tissue types including musculoskeletal tissues, the technology will open new research areas, such as largescale 3D histological phenotyping (i.e., histomics). Furthermore, 3D X-ray histology can translate directly into next-generation clinical image-based diagnostics and patient stratification using artificial intelligence and deep learning, and time-critical intraoperative 3D examination of tissue biopsies will become a realistic future target in this research programme. Here, we will present first results of our 3D Xray histology approach and portray a vision, how high-throughput and non-destructive 3D histological assessment can offer new opportunities in basic biomedical and translational research, following our ambition to provide a day-to-day imaging tool that complements and augments standard 2D histology
Schneider, Philipp
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Katsamenis, Orestis
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Thomas, Gareth
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Page, Anton M.
e315d159-536f-4d3d-83eb-5684ee42ada0
Cox, Simon
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Sinclair, Ian
6005f6c1-f478-434e-a52d-d310c18ade0d
Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Schneider, Philipp
a810f925-4808-44e4-8a4a-a51586f9d7ad
Katsamenis, Orestis
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Page, Anton M.
e315d159-536f-4d3d-83eb-5684ee42ada0
Cox, Simon
0e62aaed-24ad-4a74-b996-f606e40e5c55
Sinclair, Ian
6005f6c1-f478-434e-a52d-d310c18ade0d
Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a

Schneider, Philipp, Katsamenis, Orestis, Thomas, Gareth, Page, Anton M., Cox, Simon, Sinclair, Ian and Lackie, Peter (2019) Why every hospital should have a micro-CT: 3D x-ray histology, let’s go beyond standard 2D histology. 22nd International Workshop on Quantitative Musculoskeletal Imaging (QMSKI), , Lake Louise, Canada. 24 Feb - 01 Mar 2019.

Record type: Conference or Workshop Item (Paper)

Abstract

Living structures are an intricate threedimensional (3D) arrangement of cells and tissue matrix across many length scales. Contemporary capabilities to quantify tissue architecture, connectivity and cell relationships are however fundamentally constrained by a lack of 3D analytical platforms with appropriate resolution, penetration, structural differentiation, consistency, volumetric analysis capability and sample throughput. Structural analysis of tissues, whether for research or diagnostic purposes, remains overwhelmingly bounded and constrained by microscopic examination of relatively sparse 2D tissue sections, providing only a snapshot from which 3D spatial relationships can only be inferred. Therefore, whilst 3D medical imaging is commonplace, microscopic tissue structure analysis (i.e., histology) remains overwhelmingly wedded to 200-year-old practices of microscopic 2D examination of tissue sections. We have demonstrated previously that Xray imaging by micro-computed tomography (μCT) allows non-invasive 3D imaging of the microstructure of standard tissue biopsies 1. This yields details comparable to twodimensional (2D) optical microscope sections but for the whole tissue volume, which can for example overturn misconceptions of disease development based on 2D assessment. One exemplar is the pathogenesis of idiopathic pulmonary fibrosis 2, where 3D structural insight into co-localisation of tissue features and dysmorphia within substantive tissue volumes suggested previously unrecognised fibroblast foci plasticity. Based on this encouraging μCT results for soft tissues, in collaboration with an industrial partner, we developed a customdesign and soft-tissue optimised μCT scanner (Wellcome Trust Pathfinder Award, 2016- 17). Currently, we are establishing the foundations for routine 3D X-ray histology (Wellcome Trust Biomedical Resource and Technology Development, 2019-2022), including new X-ray equipment and standardised & automated workflows, where sample throughput will be increased and scan times reduced, providing the foundations for day-to-day 3D X-ray histology. Applicable to vast existing sample archives and a wide range of soft tissue types including musculoskeletal tissues, the technology will open new research areas, such as largescale 3D histological phenotyping (i.e., histomics). Furthermore, 3D X-ray histology can translate directly into next-generation clinical image-based diagnostics and patient stratification using artificial intelligence and deep learning, and time-critical intraoperative 3D examination of tissue biopsies will become a realistic future target in this research programme. Here, we will present first results of our 3D Xray histology approach and portray a vision, how high-throughput and non-destructive 3D histological assessment can offer new opportunities in basic biomedical and translational research, following our ambition to provide a day-to-day imaging tool that complements and augments standard 2D histology

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More information

Published date: 1 February 2019
Venue - Dates: 22nd International Workshop on Quantitative Musculoskeletal Imaging (QMSKI), , Lake Louise, Canada, 2019-02-24 - 2019-03-01

Identifiers

Local EPrints ID: 448330
URI: http://eprints.soton.ac.uk/id/eprint/448330
PURE UUID: 292abc33-a499-4879-8b1a-904042f95722
ORCID for Philipp Schneider: ORCID iD orcid.org/0000-0001-7499-3576
ORCID for Orestis Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147
ORCID for Peter Lackie: ORCID iD orcid.org/0000-0001-7138-3764

Catalogue record

Date deposited: 20 Apr 2021 16:33
Last modified: 21 Apr 2021 01:47

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Contributors

Author: Gareth Thomas
Author: Anton M. Page
Author: Simon Cox
Author: Ian Sinclair
Author: Peter Lackie ORCID iD

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