Monitoring tissue engineered constructs and protocols with laboratory-based x-ray phase contrast tomography

Savvas Savvidis; Mattia F M Gerli; Marco Pellegrini; Lorenzo Massimi; Charlotte K Hagen; Marco Endrizzi; Alessia Atzeni; Olumide K Ogunbiyi; Mark Turmaine; Elizabeth S Smith; Claudio Fagiani; Giulia Selmin; Luca Urbani; Natalie Durkin; Soichi Shibuya; Paolo De Coppi; Alessandro Olivo

doi:10.1016/j.actbio.2022.01.022

Monitoring tissue engineered constructs and protocols with laboratory-based x-ray phase contrast tomography

Acta Biomater. 2022 Mar 15:141:290-299. doi: 10.1016/j.actbio.2022.01.022. Epub 2022 Jan 18.

Authors

Savvas Savvidis¹, Mattia F M Gerli², Marco Pellegrini³, Lorenzo Massimi⁴, Charlotte K Hagen⁵, Marco Endrizzi⁶, Alessia Atzeni⁷, Olumide K Ogunbiyi⁸, Mark Turmaine⁹, Elizabeth S Smith¹⁰, Claudio Fagiani¹¹, Giulia Selmin¹², Luca Urbani¹³, Natalie Durkin¹⁴, Soichi Shibuya¹⁵, Paolo De Coppi¹⁶, Alessandro Olivo¹⁷

Affiliations

¹ Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK. Electronic address: savvas.savvides.12@ucl.ac.uk.
² Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK; UCL Division of Surgery and Interventional Science, Royal Free Hospital, London, UK. Electronic address: m.gerli@ucl.ac.uk.
³ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: marco.pellegrini@ucl.ac.uk.
⁴ Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK. Electronic address: l.massimi@ucl.ac.uk.
⁵ Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK. Electronic address: charlotte.hagen.10@ucl.ac.uk.
⁶ Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK. Electronic address: m.endrizzi@ucl.ac.uk.
⁷ Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, WC1E 6BT, UK. Electronic address: alessia.atzeni.14@ucl.ac.uk.
⁸ Department of Histopathology, Level 3, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, WC1N 3NN, UK. Electronic address: olumide.ogunbiyi@gosh.nhs.uk.
⁹ Division of Biosciences, University College London, London, WC1E 6DE, UK. Electronic address: m.turmaine@ucl.ac.uk.
¹⁰ Division of Biosciences, University College London, London, WC1E 6DE, UK. Electronic address: e.slavik-smith@ucl.ac.uk.
¹¹ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: claudio.fagiani@mail.polimi.it.
¹² Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: g.selmin@ucl.ac.uk.
¹³ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: luca.urbani@researchinliver.org.uk.
¹⁴ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: n.durkin@ucl.ac.uk.
¹⁵ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address: s.shibuya@ucl.ac.uk.
¹⁶ Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK; Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital NHS Trust, UK. Electronic address: paolo.decoppi@gosh.nhs.uk.
¹⁷ Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK. Electronic address: a.olivo@ucl.ac.uk.

PMID: 35051630
DOI: 10.1016/j.actbio.2022.01.022

Abstract

Tissue engineering (TE) aims to generate bioengineered constructs which can offer a surgical treatment for many conditions involving tissue or organ loss. Construct generation must be guided by suitable assessment tools. However, most current tools (e.g. histology) are destructive, which restricts evaluation to a single-2D anatomical plane, and has no potential for assessing constructs prior to or following their implantation. An alternative can be provided by laboratory-based x-ray phase contrast computed tomography (PC-CT), which enables the extraction of 3D density maps of an organ's anatomy. In this work, we developed a semi-automated image processing pipeline dedicated to the analysis of PC-CT slices of oesophageal constructs. Visual and quantitative (density and morphological) information is extracted on a volumetric basis, enabling a comprehensive evaluation of the regenerated constructs. We believe the presented tools can enable the successful regeneration of patient-specific oesophagus, and bring comparable benefit to a wide range of TE applications. STATEMENT OF SIGNIFICANCE: Phase contrast computed tomography (PC-CT) is an imaging modality which generates high resolution volumetric density maps of biological tissue. In this work, we demonstrate the use of PC-CT as a new tool for guiding the progression of an oesophageal tissue engineering (TE) protocol. Specifically, we developed a semi-automated image-processing pipeline which analyses the oesophageal PC-CT slices, extracting visual and quantitative (density and morphological) information. This information was proven key for performing a comprehensive evaluation of the regenerated constructs, and cannot be obtained through existing assessment tools primarily due to their destructive nature (e.g. histology). This work paves the way for using PC-CT in a wide range of TE applications which can be pivotal for unlocking the potential of this field.

Keywords: 3D-imaging; In-vitro organ maturation; Laboratory-based phase contrast computed tomography (PC-CT); Regenerative medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Image Processing, Computer-Assisted
Microscopy, Phase-Contrast
Tissue Engineering* / methods
Tomography, X-Ray Computed* / methods
X-Rays

Grants and funding

NIHR-RP-2014-04-046/DH_/Department of Health/United Kingdom