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The spatiotemporal spread of cervical spinal cord contusion injury pathology revealed by 3D in-line phase contrast synchrotron X-ray microtomography

DOI: 10.1016/j.expneurol.2020.113529 DOI Help

Authors: Merrick C. Strotton (King's College London) , Andrew J. Bodey (Diamond Light Source) , Kazimir Wanelik (Diamond Light Source) , Carl Hobbs (King's College London) , Christoph Rau (Diamond Light Source) , Elizabeth J. Bradbury (King's College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Experimental Neurology

State: Published (Approved)
Published: November 2020
Diamond Proposal Number(s): 14907 , 18417

Open Access Open Access

Abstract: Extensive structural changes occur within the spinal cord following traumatic injury. Acute tissue debris and necrotic tissue are broken down, proliferating local glia and infiltrating leukocytes remodel tissue biochemical and biophysical properties, and a chronic cavity surrounded by a scar forms at the injury epicentre. Serial-section 2D histology has traditionally assessed these features in experimental models of spinal cord injury (SCI) to measure the extent of tissue pathology and evaluate efficacy of novel therapies. However, this 2D snapshot approach overlooks slice intervening features, with accurate representation of tissue compromised by mechanical processing artefacts. 3D imaging avoids these caveats and allows full exploration of the injured tissue volume to characterise whole tissue pathology. Amongst 3D imaging modalities, Synchrotron Radiation X-ray microtomography (SRμCT) is advantageous for its speed, ability to cover large tissue volumes at high resolution, and need for minimal sample processing. Here we demonstrate how extended lengths of formalin-fixed, paraffin-embedded (FFPE) rat spinal cord can be completely imaged by SRμCT with micron resolution. Label-free contrast derived from X-ray phase interactions with low-density soft tissues, reveals spinal cord white matter, gray matter, tissue damage and vasculature, with tissue still viable for targeted 2D-histology after 3D imaging. We used SRμCT to quantify tissue pathology after a midline, cervical level (C6), 225 kDyne contusion injury over acute-to-chronic (24 h to 5 weeks) post injury time points. Quantification revealed acute tissue swelling prior to chronic atrophy across the whole imaged region (spanning 2 spinal segments above and below injury), along with rostro-caudal asymmetries in white and gray matter volume loss. 3D volumes revealed satellite damage in tissue far removed from the epicentre, and extensive rostro-caudal spread of damage through the base of the dorsal columns at 24 h post injury. This damage overlapped regions of vasogenic oedema, confirmed with subsequent histology. Tissue damage at later time points in border regions was most prominent in the dorsal columns, where it overlapped sites of damaged venous vasculature. Elaborating rostro-caudal and spatiotemporal asymmetries in reduced traumatic injury models centred on these regions may inform future treatments that seek to limit the spread of tissue pathology to these ‘at-risk’ regions.

Journal Keywords: Synchrotron; Microtomography; Spinal cord injury; Neurotrauma; White matter; Gray matter

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I13-2-Diamond Manchester Imaging

Added On: 23/11/2020 13:35


Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery

Technical Tags:

Imaging Tomography