OUR VISION…
Located within the Biomedical Imaging Unit at University Hospital Southampton, we are uniquely positioned in a clinical setting that boosts the visibility and accessibility of the XRH technology for clinical and biomedical research users.
Our aim is to push the boundaries of 3D X-ray histology (XRH) imaging and transition this innovative technology into clinical applications. By enriching clinical practice and biomedical imaging research with non-destructive 3D imaging of biological tissues, we seek to revolutionise histology workflows.
Our vision includes diffusing XRH technology to support both clinical and preclinical applications, enhancing the quality and precision of medical diagnostics and research. Ultimate aim is to better patient outcomes and a contribute in improving our understanding of complex biological systems.
In alignment with our University’s commitment to the Triple Helix model, which intertwines education, research, and knowledge exchange and enterprise (KEE), we place people (our team and users) at the heart of all we do. We inspire excellence and we focus our efforts on achieving remarkable outcomes for our users. Our core and wider team drive our impact on both local and global level, though a combination of education, cutting-edge research, and knowledge exchange.
OUR STORY…
FIRST STEPS
3D X-ray Histology (XRH) is based on the proof-of-principle study we published in 2015 [Scott et al.] initiated by Katherine Seal, a medical student and Dr Anna Scott funded by an IfLS Interdisciplinary ‘Bridging the Gap’ scheme. XRH integrates the results of more than five-years continuous development of hardware, imaging/visualisation protocols and workflow.This provides 3D visualisation compatible with both the current clinical histology workflow and archived samples.
Image matching of μCT and histological section stained with Movat’s Pentachrome [Scott et al., 2015]
First research applications
In 2016, samples from patients with idiopathic lung fibrosis were used to characterize the shape and interrelationships of areas of fibrosis in 3D, demonstrating the value of non-destructive 3D (volume) imaging by micro-CT. Working with the team, Dr Mark Jones, Prof Luca Richeldi and colleagues identified fibrotic structures with large variations in shape and volume, suggesting previously unrecognized plasticity that could not be identified using current ‘gold standard’ 2D histology (Jones et al., 2016; also see video below).
Simultaneously, work with Dr Tillie Hackett from the James Hogg Research Centre (University of British Columbia) provided important insights into the pathogenesis of chronic obstructive pulmonary disease (COPD) published in The Lancet Respiratory Medicine (Koo et al, 2018). This demonstrated:
‣ The capability to image standard formalin-fixed paraffin-embedded (FFPE) tissue samples, providing access to extensive archives of diagnostic tissue
‣ How volumetric μCT-base XRH enhances the understanding of disease pathology
‣ The value of XRH guided histological sectioning in supporting correlative imaging
Nikon Med-X (prototype) – a soft tissue X-ray histology prototype
The first studies listed above were conducted using engineering scanners and a unique highly versatile heavy-duty walk-in experimental μCT chamber, equipped with multiple micro-focus X-ray sources and detectors.
These systems provided the flexibility needed to optimise imaging conditions, and establish the proof-of-principle. However, the sheer size, cost and designs specifications of such systems are would render the technique unrealistic as a histology tool for research or clinical diagnistics.
Med-X (prototype)
The Med-X prototype μCT system was developed as part of a Wellcome Trust Pathfinder* project in close collaboration with Nikon X-Tek Systems Ltd. In essence Med-X is a ‘distilled’ version of its engineering ‘ancestor’, specifically designed and further optimised for use with soft tissue in a medical research/clinical environment.
Proof of utility and a robust and detailed workflow was demonstrated in our recent paper [Katsamenis et al, Am. J. Pathol] specifically aligned with the use of routinely prepared paraffin embedded tissue samples.
* Wellcome Trust/Pathfinder, 2016 -2017, Development of micro-computed tomography (μCT) for enhanced diagnosis and prognosis in interstitial lung diseases (ILD)
Foundations for routine 3D X-ray histology
The impact of 3D X-ray histology on respiratory research, first showcased in our Wellcome Trust Pathfinder project (see publications page) was further advanced through a Wellcome Trust Technology Development Grant-funded initiative: “Foundations for Routine 3D X-ray Histology”. During this project we developed hardware, software and workflows to:
‣ extend the range of tissues and sample types that can be scanned
‣ significantly increase throughput, reducing scan times and cost per scan
‣ standardise image acquisition and processing workflows and
‣ raise awareness and drive uptake of 3D X-ray histology (XRH)
Advantages of XRH
- Micrometer resolution 3D: Visualise and quantify microstructure soft tissue in their 3D context.
- Non-destructive: Can be combined with specific 2D histology techniques, including histochemistry, immunocytochemistry, in situ hybridization
- Volume imaging of tissue heterogeneity; Improve understanding of disease initiation and progression in 3D.
- Histomics: Help identify new microstructural hallmarks of disease.
- Formalin fixed paraffin embedded samples: Imaging archival material stored in many hospitals and tissue banks will allowing validation of microstructural hallmarks of disease
- Fully digital 3D: XRH coupled with artificial intelligence/computer-aided diagnosis, could improve diagnostic accuracy and support patient stratification.
Video 1. Simultaneous visualization of a single μCT and hematoxylin and eosin histology slice. Coregistration of histology with μCT image data and simultaneous visualization of both data sets allow for direct comparison of the two imaging modalities and precise, histology-guided identification of a wide range of tissue structures and diagnostically relevant histologic criteria | [Katsamenis et al, Am. J. Pathol]
Video 2: Orthogonal plane view and arbitrary virtual slicing. Orthogonal planes of the μCT data can also be viewed immediately after CT reconstruction for analyzing the spatial arrangements of tissue (micro)structures, their orientation, as well as heterogeneity and connectivity in (3D) space. An example of such an interactive assessment of 3D data is shown herein, where the reviewer locates a blood vessel and examines the cross-sectional views along two orthogonal planes. | [Katsamenis et al, Am. J. Pathol]
Foundations for routine 3D X-ray histology (XRH) project team – (2018 -2022)
