Development of a cardiovascular magnetic resonance-compatible large animal isolated heart model for direct comparison of beating and arrested hearts

Andrew D Scott, Vito Domenico Bruno, Dennis J Doorly, Dudley J Pennell, Raimondo Ascione, Ranil de Silva*, David N Firmin, Jan N Rose, Padmini Sarathchandra, Karen P McCarthy, Malte Roehl, Sonia Nialles-Vallespin, Pedro F Ferreira, Rasheda A. Chowdhury, Lale Begum, Ben Pardoe, Margarita Gorodezky, Zohya Khalique, Tim Jackson

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
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Abstract

Background
Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here we develop a CMR compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states.

Methods
10 porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers.

Results
Regular sustained contraction was successfully established in 6/10 hearts, including the final 5 hearts. Imaging was performed in 4 hearts and one underwent the full protocol including co-localised histology. Image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2, DT-CMR measures and an increase in mass was consistent with development of myocardial edema resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5μm histological sections at and a 100μm thick section showing cell morphology on 3D fluorescent confocal microscopy co-localised to DT-CMR data were obtained.

Conclusions
A CMR compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent co-localised histology without the need for onsite pre-clinical facilities.
Original languageEnglish
Article numbere4692
JournalNMR in Biomedicine
Volume35
Issue number7
DOIs
Publication statusPublished - 17 Jan 2022

Bibliographical note

Funding Information:
The authors would like to acknowledge the contribution of: Alex Berry in 3D printing the perfusion chamber; Robin Hardie, Clinical Engineering, Royal Brompton Hospital, for assistance in engineering the perfusion chamber; Linda Hammond at Barts Cancer Institute for assistance with scanning slides; the Imperial College Facility for Light Imaging Microscopy for assistance with 3D confocal microscopy; the staff of the CMR Unit, Royal Brompton Hospital; and the staff at the TBRC, University of Bristol. This work was supported by British Heart Foundation (BHF) grants (RG/19/1/34160, RE/13/4/30184, PG/14/68/30798) and an Institute of Physics and Engineering in Medicine Research and Innovation Award. RA acknowledges funding support from the BHF (IG/14/2/30991, PG/16/104/32652), the Medical Research Council (MR/L012723/1) and from the Bristol National Institute for Health Research Biomedical Research Centre. RAC acknowledges funding from a BHF grant (PG/16/17/32069) and a Rosetrees Trust Grant (JS15/M645). Note that the CMR Unit, Royal Brompton Hospital, receives research support from Siemens. Siemens had no specific role in this study.

Publisher Copyright:
© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

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