3D X-ray histology: micro-CT goes medical

Schneider, P. (2019) 3D X-ray histology: micro-CT goes medical. In Annual Congress of the European Society of Biomechanics (ESB) Book of Abstracts. Mondial Congress & Events..

Record type: Conference or Workshop Item (Paper)

Abstract

Background Living structures are an intricate three-dimensional (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. Recent advances We have demonstrated previously that X-ray imaging by micro-computed tomography (μCT) allows non-invasive 3D imaging of the microstructure of standard tissue biopsies [1]. This yields details comparable to two-dimensional (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 custom-design and soft-tissue optimised μCT scanner [3]. Currently, we are establishing the foundations for routine 3D X-ray histology [4], 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. Future directions 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 large-scale 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 X-ray 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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