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Development of a CMR compatible large animal isolated heart model for direct comparison of beating and arrested hearts

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Title: Development of a CMR compatible large animal isolated heart model for direct comparison of beating and arrested hearts
Authors: Scott, A
Jackson, T
Khalique, Z
Gorodezky, M
Pardoe, B
Begum, L
Bruno, VD
Chowdhury, R
Ferreira, P
Nielles-Vallespin, S
Roehl, M
McCarthy, K
Sarathchandra, P
Rose, J
Doorly, D
Pennell, D
Ascione, R
De Silva, PER
Firmin, D
Item Type: Journal Article
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.
Issue Date: 17-Jan-2022
Date of Acceptance: 7-Jan-2022
URI: http://hdl.handle.net/10044/1/94262
DOI: 10.1002/nbm.4692
ISSN: 0952-3480
Publisher: John Wiley and Sons
Journal / Book Title: NMR in Biomedicine
Volume: 35
Issue: 7
Copyright Statement: © 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: British Heart Foundation
Heart Research UK
British Heart Foundation
British Heart Foundation
British Heart Foundation
Funder's Grant Number: RE/13/4/30184
RG2648/15/18
RG/19/1/34160
RG/19/1/34160
PG/14/68/30798
Keywords: Science & Technology
Life Sciences & Biomedicine
Technology
Biophysics
Radiology, Nuclear Medicine & Medical Imaging
Spectroscopy
cardiovascular magnetic resonance
diffusion tensor imaging
Langendorff perfusion
microstructure
myocardial tissue characterization
oedema
preclinical
ISOLATED RAT-HEART
ISOLATED PIG-HEART
DIFFUSION-TENSOR
IN-VIVO
SPIN-ECHO
P-31 NMR
MOTION
LANGENDORFF
PERFUSION
ISCHEMIA
Langendorff perfusion
cardiovascular magnetic resonance
diffusion tensor imaging
microstructure
myocardial tissue characterization
oedema
preclinical
Animals
Heart
Heart Transplantation
Humans
Magnetic Resonance Imaging, Cine
Magnetic Resonance Spectroscopy
Myocardium
Swine
Tissue Donors
Myocardium
Heart
Animals
Swine
Humans
Magnetic Resonance Imaging, Cine
Heart Transplantation
Magnetic Resonance Spectroscopy
Tissue Donors
0304 Medicinal and Biomolecular Chemistry
0903 Biomedical Engineering
1103 Clinical Sciences
Nuclear Medicine & Medical Imaging
Publication Status: Published online
Online Publication Date: 2022-01-17
Appears in Collections:National Heart and Lung Institute
Aeronautics
Faculty of Medicine
Faculty of Engineering