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      Histological validation of cardiovascular magnetic resonance T1 mapping markers of myocardial fibrosis in paediatric heart transplant recipients

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          Abstract

          Background

          Adverse fibrotic remodeling is detrimental to myocardial health and a reliable method for monitoring the development of fibrotic remodeling may be desirable during the follow-up of patients after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) has been increasingly applied and validated histologically in adult patients with heart disease. However, comparisons of CMR findings with histological fibrosis burden in children are lacking. This study aimed to compare native T1 times and extracellular volume fraction (ECV) derived from CMR with the degree of collagen on endomyocardial biopsy (EmBx), and to investigate the association between myocardial fibrosis and clinical as well as functional markers in children after HTx.

          Methods

          EmBx and CMR were performed on the same day. All specimens were stained with picrosirius red. The collagen volume fraction (CVF) was calculated as ratio of stained collagen area to total myocardial area on EmBx. Native T1 values and ECV were measured by CMR on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach.

          Results

          Twenty patients (9.9 ± 6.2 years of age; 9 girls) after HTx were prospectively enrolled, at a median of 1.3 years (0.02–12.6 years) post HTx, and compared to 24 controls (13.9 ± 2.6 years of age; 12 girls). The mean histological CVF was 10.0 ± 3.4%. Septal native T1 times and ECV were higher in HTx patients compared to controls (1008 ± 32 ms vs 979 ± 24 ms, p < 0.005 and 0.30 ± 0.03 vs 0.22 ± 0.03, p < 0.0001, respectively). CVF showed a moderate correlation with native T1 ( r = 0.53, p < 0.05) as well as ECV ( r = 0.46, p < 0.05). Native T1 time, but not ECV and CVF, correlated with ischemia time ( r = 0.46, p < 0.05).

          Conclusions

          CMR-derived fibrosis markers correlate with histological degree of fibrosis on EmBx in children after HTx. Further, native T1 times are associated with longer ischemia times.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12968-017-0326-x) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association.

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            T1 Mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy.

            To determine the utility of cardiac magnetic resonance (MR) T1 mapping for quantification of diffuse myocardial fibrosis compared with the standard of endomyocardial biopsy. This HIPAA-compliant study was approved by the institutional review board. Cardiomyopathy patients were retrospectively identified who had undergone endomyocardial biopsy and cardiac MR at one institution during a 5-year period. Forty-seven patients (53% male; mean age, 46.8 years) had undergone diagnostic cardiac MR and endomyocardial biopsy. Thirteen healthy volunteers (54% male; mean age, 38.1 years) underwent cardiac MR as a reference. Myocardial T1 mapping was performed 10.7 minutes ± 2.7 (standard deviation) after bolus injection of 0.2 mmol/kg gadolinium chelate by using an inversion-recovery Look-Locker sequence on a 1.5-T MR imager. Late gadolinium enhancement was assessed by using gradient-echo inversion-recovery sequences. Cardiac MR results were the consensus of two radiologists who were blinded to histopathologic findings. Endomyocardial biopsy fibrosis was quantitatively measured by using automated image analysis software with digital images of specimens stained with Masson trichrome. Histopathologic findings were reported by two pathologists blinded to cardiac MR findings. Statistical analyses included Mann-Whitney U test, analysis of variance, and linear regression. Median myocardial fibrosis was 8.5% (interquartile range, 5.7-14.4). T1 times were greater in control subjects than in patients without and in patients with evident late gadolinium enhancement (466 msec ± 14, 406 msec ± 59, and 303 msec ± 53, respectively; P < .001). T1 time and histologic fibrosis were inversely correlated (r = -0.57; 95% confidence interval: -0.74, -0.34; P < .0001). The area under the curve for myocardial T1 time to detect fibrosis of greater than 5% was 0.84 at a cutoff of 383 msec. Cardiac MR with T1 mapping can provide noninvasive evidence of diffuse myocardial fibrosis in patients referred for evaluation of cardiomyopathy. © RSNA, 2012.
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              Society for Cardiovascular Magnetic Resonance guidelines for reporting cardiovascular magnetic resonance examinations

              These reporting guidelines are recommended by the Society for Cardiovascular Magnetic Resonance (SCMR) to provide a framework for healthcare delivery systems to disseminate cardiac and vascular imaging findings related to the performance of cardiovascular magnetic resonance (CMR) examinations.
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                Author and article information

                Contributors
                seiko.ide@sickkids.ca
                JenRiesenkampff@gmx.net
                david.chiasson@sickkids.ca
                anne.dipchand@sickkids.ca
                paul.kantor@albertahealthservices.ca
                rajiv.chaturvedi@sickkids.ca
                shi-joon.yoo@sickkids.ca
                +1-416-813-7654 , lars.grosse-wortmann@sickkids.ca
                Journal
                J Cardiovasc Magn Reson
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central (London )
                1097-6647
                1532-429X
                1 February 2017
                1 February 2017
                2017
                : 19
                : 10
                Affiliations
                [1 ]GRID grid.17063.33, Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, , University of Toronto, ; 555 University Avenue, Toronto, ON M5G 1X8 Canada
                [2 ]GRID grid.17063.33, Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, , University of Toronto, ; Toronto, ON Canada
                [3 ]ISNI 0000 0004 0633 3703, GRID grid.416656.6, , Division of Cardiology, Department of Paediatrics, Stollery Children’s Hospital, ; Edmonton, AB Canada
                [4 ]GRID grid.17063.33, Department of Diagnostic Imaging, The Hospital for Sick Children, , University of Toronto, ; Toronto, ON Canada
                Author information
                http://orcid.org/0000-0002-1185-3805
                Article
                326
                10.1186/s12968-017-0326-x
                5286863
                28143545
                f1f95c9a-8a7f-4968-950a-926142e3679b
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 August 2016
                : 13 January 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007263, Astellas Foundation for Research on Metabolic Disorders;
                Award ID: K1096
                Award Recipient :
                Funded by: Labatt Family Heart Centre
                Award ID: none
                Award Recipient :
                Funded by: Siemens Healthcare
                Award ID: none
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Cardiovascular Medicine
                paediatric heart transplantation,diffuse myocardial fibrosis,cardiovascular magnetic resonance,native t1 time,extracellular volume fraction,histological validation

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