Extracellular volume imaging by MRI provides insight into overt and subclinical myocardial pathology

Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services, 10 Center Drive, Bethesda, MD 20892-1061, USA.
European Heart Journal (Impact Factor: 15.2). 01/2012; 33(10):1268-78. DOI: 10.1093/eurheartj/ehr481
Source: PubMed


Conventional late gadolinium enhancement (LGE) cardiac magnetic resonance can detect myocardial infarction and some forms of non-ischaemic myocardial fibrosis. However, quantitative imaging of extracellular volume fraction (ECV) may be able to detect subtle abnormalities such as diffuse fibrosis or post-infarct remodelling of remote myocardium. The aims were (1) to measure ECV in myocardial infarction and non-ischaemic myocardial fibrosis, (2) to determine whether ECV varies with age, and (3) to detect sub-clinical abnormalities in 'normal appearing' myocardium remote from regions of infarction.
Cardiac magnetic resonance ECV imaging was performed in 126 patients with T1 mapping before and after injection of gadolinium contrast. Conventional LGE images were acquired for the left ventricle. In patients with a prior myocardial infarction, the infarct region had an ECV of 51 ± 8% which did not overlap with the remote 'normal appearing' myocardium that had an ECV of 27 ± 3% (P < 0.001, n = 36). In patients with non-ischaemic cardiomyopathy, the ECV of atypical LGE was 37 ± 6%, whereas the 'normal appearing' myocardium had an ECV of 26 ± 3% (P < 0.001, n = 30). The ECV of 'normal appearing' myocardium increased with age (r = 0.28, P = 0.01, n = 60). The ECV of 'normal appearing' myocardium remote from myocardial infarctions increased as left ventricular ejection fraction decreased (r = -0.50, P = 0.02).
Extracellular volume fraction imaging can quantitatively characterize myocardial infarction, atypical diffuse fibrosis, and subtle myocardial abnormalities not clinically apparent on LGE images. Taken within the context of prior literature, these subtle ECV abnormalities are consistent with diffuse fibrosis related to age and changes remote from infarction.

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    • "Edema has been little studied to date. ECV imaging can quantitatively characterize infarcted scar and atypical fibrosis, diffuse myocardial abnormalities — even when not clinically apparent on LGE images — and also the small changes occurring in myocardium with aging, even if near to detection limit [35••, 36]. "
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    ABSTRACT: Heart failure (HF) is a major and growing cause of morbidity and mortality. Despite initial successes, there have been few recent therapeutic advances. A better understanding of HF pathophysiology is needed with renewed focus on the myocardium itself. A new imaging technique is now available that holds promise. T1 mapping is a cardiovascular magnetic resonance (CMR) technique for non-invasive myocardial tissue characterization. T1 alters with disease. Pre-contrast (native) T1 changes with a number of processes such as fibrosis, edema and infiltrations. If a post contrast scan is also done, the extracellular volume fraction (ECV) can be measured, a direct measure of the interstitium and its reciprocal, the cell volume. This dichotomy is fundamental - and now measurable promising more targeted therapy and new insights into disease biology.
    Current Cardiovascular Imaging Reports 09/2014; 7(9):9287. DOI:10.1007/s12410-014-9287-8
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    • "Already, several centers have begun exploring the role of ECV as a novel imaging biomarker of diffuse myocardial fibrosis among those with HCM. From a diagnostic standpoint, Ugander et al [39], Sado et al [40], and Kellman et al [41], all demonstrated the ability of abnormally elevated ECV measurement to discriminate between myocardial regions (and individuals) of health vs disease. Our group has observed a preliminary association between ECV and BNP [42], of interest given the recent observation that BNP may be a relevant HCM disease severity marker [43]. "
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    ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a cardiovascular genetic disease with a varied clinical presentation and phenotype. Although mutations are typically found in genes coding for sarcomeric proteins, phenotypic derangements extend beyond the myocyte to include the extracellular compartment. Myocardial fibrosis is commonly detected by histology, and is associated with clinical vulnerability to adverse outcomes. Over the past decade, the noninvasive visualization of myocardial fibrosis by cardiovascular magnetic resonance (CMR) techniques has garnered much interest given the potential applications toward improving our understanding of pathophysiologic mechanisms of disease, as well as diagnosis and prognosis. Late gadolinium enhancement (LGE) imaging techniques are able to detect focal (typically replacement) fibrosis. Newer CMR techniques that measure absolute T1 relaxation time allow the quantification of the entire range of focal to diffuse (interstitial) fibrosis and may overcome potential limitations of LGE. This review will discuss the methodology and current status of these novel techniques, with a focus on extracellular volume fraction (ECV). Recent findings describing ECV measurement in HCM will be summarized.
    Current Cardiovascular Imaging Reports 05/2014; 7(5):9267. DOI:10.1007/s12410-014-9267-z
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    • "The major outcome of this CMR study using T1 mapping was that in hypertrophic cardiomyopathy areas without late gadolinium enhancement showed a similar extracellular volume fraction (ECV) compared to controls. This is in line with a study by Ugander et al. [17], who reported non-elevated ECV in ‘normal appearing’ myocardium in non-ischemic cardiomyopathies. Study results are not directly comparable however, since the patient population in present study was defined more precisely (HCM only) and thresholding was used to select ROI’s in LGE positive HCM patients instead of visual interpretation. "
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    ABSTRACT: In hypertrophic cardiomyopathy (HCM), autopsy studies revealed both increased focal and diffuse deposition of collagen fibers. Late gadolinium enhancement imaging (LGE) detects focal fibrosis, but is unable to depict interstitial fibrosis. We hypothesized that with T1 mapping, which is employed to determine the myocardial extracellular volume fraction (ECV), can detect diffuse interstitial fibrosis in HCM patients. T1 mapping with a modified Look-Locker Inversion Recovery (MOLLI) pulse sequence was used to calculate ECV in manifest HCM (n = 16) patients and in healthy controls (n = 14). ECV was determined in areas where focal fibrosis was excluded with LGE. The total group of HCM patients showed no significant changes in mean ECV values with respect to controls (0.26 +/- 0.03 vs 0.26 +/- 0.02, p = 0.83). Besides, ECV in LGE positive HCM patients was comparable with LGE negative HCM patients (0.27 +/- 0.03 vs 0.25 +/- 0.03, p = 0.12). This study showed that HCM patients have a similar ECV (e.g. interstitial fibrosis) in myocardium without LGE as healthy controls. Therefore, the additional clinical value of T1 mapping in HCM seems limited, but future larger studies are needed to establish the clinical and prognostic potential of this new technique within HCM.
    Journal of Cardiovascular Magnetic Resonance 04/2014; 16(1):28. DOI:10.1186/1532-429X-16-28 · 4.56 Impact Factor
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