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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.

      Related collections

      Most cited references 27

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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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        ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.

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          Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans.

          Diffuse myocardial fibrosis is a final end point in most cardiac diseases. It is missed by the cardiovascular magnetic resonance (CMR) late gadolinium enhancement technique. Currently, quantifying diffuse myocardial fibrosis requires invasive biopsy, with inherent risk and sampling error. We have developed a robust and noninvasive technique, equilibrium contrast CMR (EQ-CMR) to quantify diffuse fibrosis and have validated it against the current gold standard of surgical myocardial biopsy. The 3 principles of EQ-CMR are a bolus of extracellular gadolinium contrast followed by continuous infusion to achieve equilibrium; a blood sample to measure blood volume of distribution (1-hematocrit); and CMR to measure pre- and postequilibrium T1 (with heart rate correction). The myocardial volume of distribution is calculated, reflecting diffuse myocardial fibrosis. Clinical validation occurred in patients undergoing aortic valve replacement for aortic stenosis or myectomy in hypertrophic cardiomyopathy (n=18 and n=8, respectively). Surgical biopsies were analyzed for picrosirius red fibrosis quantification on histology. The mean histological fibrosis was 20.5+/-11% in aortic stenosis and 17.1+/-7.4% in hypertrophic cardiomyopathy. EQ-CMR correlated strongly with biopsy histological fibrosis: aortic stenosis, r(2)=0.86, Kendall Tau coefficient (T)=0.71, P<0.001; hypertrophic cardiomyopathy, r(2)=0.62, T=0.52, P=0.08; combined r(2)=0.80, T=0.67, P<0.001. We have developed and validated a new technique, EQ-CMR, to measure diffuse myocardial fibrosis as an add-on to a standard CMR scan, which allows for the noninvasive quantification of the diffuse fibrosis burden in myocardial diseases.
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            Author and article information

            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
            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
            23349348
            3686317
            heartjnl-2012-303052
            10.1136/heartjnl-2012-303052
            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/

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            1506
            Cardiovascular Imaging
            Original article
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            Cardiovascular Medicine

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