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      Human non-contrast T1 values and correlation with histology in diffuse fibrosis

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          Abstract

          Background

          Aortic stenosis (AS) leads to diffuse fibrosis in the myocardium, which is linked to adverse outcome. Myocardial T1 values change with tissue composition.

          Objective

          To test the hypothesis that our recently developed non-contrast cardiac magnetic resonance (CMR) T1 mapping sequence could identify myocardial fibrosis without contrast agent.

          Design, setting and patients

          A prospective CMR non-contrast T1 mapping study of 109 patients with moderate and severe AS and 33 age- and gender-matched controls.

          Methods

          CMR at 1.5 T, including non-contrast T1 mapping using a shortened modified Look–Locker inversion recovery sequence, was carried out. Biopsy samples for histological assessment of collagen volume fraction (CVF%) were obtained in 19 patients undergoing aortic valve replacement.

          Results

          There was a significant correlation between T1 values and CVF% (r=0.65, p=0.002). Mean T1 values were significantly longer in all groups with severe AS (972±33 ms in severe asymptomatic, 1014±38 ms in severe symptomatic) than in normal controls (944±16 ms) (p<0.05). The strongest associations with T1 values were for aortic valve area (r=−0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008), and these were the only independent predictors on multivariate analysis.

          Conclusions

          Non-contrast T1 values are increased in patients with severe AS and further increase in symptomatic compared with asymptomatic patients. T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future.

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          Most cited references32

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          Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy.

          We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy.
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            Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart.

            A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of < 200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd-DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath-hold. Copyright 2004 Wiley-Liss, Inc.
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              Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping.

              The purpose of this study was to investigate a noninvasive method for quantifying diffuse myocardial fibrosis with cardiac magnetic resonance imaging (CMRI). Diffuse myocardial fibrosis is a fundamental process in pathologic remodeling in cardiomyopathy and is postulated to cause increased cardiac stiffness and poor clinical outcomes. Although regional fibrosis is easily imaged with cardiac magnetic resonance, there is currently no noninvasive method for quantifying diffuse myocardial fibrosis. We performed CMRI on 45 subjects (25 patients with heart failure, 20 control patients), on a clinical 1.5-T CMRI scanner. A prototype T(1) mapping sequence was used to calculate the post-contrast myocardial T(1) time as an index of diffuse fibrosis; regional fibrosis was identified by delayed contrast enhancement. Regional and global systolic function was assessed by cine CMRI in standard short- and long-axis planes, with echocardiography used to evaluate diastology. An additional 9 subjects underwent CMRI and endomyocardial biopsy for histologic correlation. Post-contrast myocardial T(1) times correlated histologically with fibrosis (R = -0.7, p = 0.03) and were shorter in heart failure subjects than controls (383 +/- 17 ms vs. 564 +/- 23 ms, p < 0.0001). The T(1) time of heart failure myocardium was shorter than that in controls even when excluding areas of regional fibrosis (429 +/- 22 ms vs. 564 +/- 23 ms, p < 0.0001). The post-contrast myocardial T(1) time shortened as diastolic function worsened (562 +/- 24 ms in normal diastolic function vs. 423 +/- 33 ms in impaired diastolic function vs. 368 +/- 20 ms in restrictive function, p < 0.001). Contrast-enhanced CMRI T(1) mapping identifies changes in myocardial T(1) times in heart failure, which appear to reflect diffuse fibrosis.
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                Author and article information

                Journal
                Heart
                Heart
                heartjnl
                heart
                Heart
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1355-6037
                1468-201X
                1 July 2013
                24 January 2013
                : 99
                : 13
                : 932-937
                Affiliations
                [1 ]Department of Cardiovascular Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research , University of Oxford , Oxford, UK
                [2 ]Heart Hospital Imaging Centre, Institute of Cardiovascular Science, University College London , London, UK
                [3 ]Oxford Heart Centre, John Radcliffe Hospital , Oxford, UK
                Author notes
                [Correspondence to ] Dr Saul G Myerson, Department of Cardiovascular Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Level 0, Headley Way, Oxford OX3 9DU, UK; saul.myerson@ 123456cardiov.ox.ac.uk
                Article
                heartjnl-2012-303052
                10.1136/heartjnl-2012-303052
                3686317
                23349348
                df1fee73-d9c6-4faf-9eb1-607293f479a7
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 1 October 2012
                : 27 November 2012
                : 11 December 2012
                Categories
                1506
                Cardiovascular Imaging
                Original article
                Custom metadata
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                Cardiovascular Medicine
                Cardiovascular Medicine

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