Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR

Journal of Cardiovascular Magnetic Resonance (Impact Factor: 4.56). 12/2012; 14(1):88. DOI: 10.1186/1532-429X-14-88
Source: PubMed


Myocardial extracellular volume (ECV) is elevated in fibrosis or infiltration and can be quantified by measuring the haematocrit with pre and post contrast T1 at sufficient contrast equilibrium. Equilibrium CMR (EQ-CMR), using a bolus-infusion protocol, has been shown to provide robust measurements of ECV using a multibreath-hold T1 pulse sequence. Newer, faster sequences for T1 mapping promise whole heart coverage and improved clinical utility, but have not been validated.

Multibreathhold T1 quantification with heart rate correction and single breath-hold T1 mapping using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) were used in equilibrium contrast CMR to generate ECV values and compared in 3 ways.Firstly, both techniques were compared in a spectrum of disease with variable ECV expansion (n=100, 50 healthy volunteers, 12 patients with hypertrophic cardiomyopathy, 18 with severe aortic stenosis, 20 with amyloid). Secondly, both techniques were correlated to human histological collagen volume fraction (CVF%, n=18, severe aortic stenosis biopsies). Thirdly, an assessment of test:retest reproducibility of the 2 CMR techniques was performed 1 week apart in individuals with widely different ECVs (n=10 healthy volunteers, n=7 amyloid patients).

More patients were able to perform ShMOLLI than the multibreath-hold technique (6% unable to breath-hold). ECV calculated by multibreath-hold T1 and ShMOLLI showed strong correlation (r(2)=0.892), little bias (bias -2.2%, 95%CI -8.9% to 4.6%) and good agreement (ICC 0.922, range 0.802 to 0.961, p<0.0001). ECV correlated with histological CVF% by multibreath-hold ECV (r(2)= 0.589) but better by ShMOLLI ECV (r(2)= 0.685). Inter-study reproducibility demonstrated that ShMOLLI ECV trended towards greater reproducibility than the multibreath-hold ECV, although this did not reach statistical significance (95%CI -4.9% to 5.4% versus 95%CI -6.4% to 7.3% respectively, p=0.21).

ECV quantification by single breath-hold ShMOLLI T1 mapping can measure ECV by EQ-CMR across the spectrum of interstitial expansion. It is procedurally better tolerated, slightly more reproducible and better correlates with histology compared to the older multibreath-hold FLASH techniques.

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Available from: James C Moon, May 10, 2014
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    • "In a single breath-hold, using various approaches, a T1 colour relaxation map is made [11–13]. Within the map, each given pixel value directly corresponds its underlying relaxation time that can be seen (in colour) or more formally measured, standardized, calibrated to histology [14••, 15, 16], compared across diseases and with normal reference ranges [17]. There are two key ways of using T1 mapping: without or before contrast (native T1 mapping); and with contrast, typically by subtracting the pre and post maps with hematocrit correction to generate the extracellular volume fraction (ECV) (Fig. 1). "
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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.
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    • "Flett et al [34] reported excellent correlation (R2 = 0.86) between ECV and collagen volume fraction in a cohort of patients with either aortic stenosis or hypertrophic cardiomyopathy. Fontana et al [35] and White et al [36] both demonstrated good correlations with quantitative histology using variations on the ECV technique in a wider spectrum of patients with aortic stenosis, hypertrophic cardiomyopathy, amyloid, chronic myocardial infarction. Miller et al also described robust agreement in an elegant, comprehensive study of whole heart validation of ECV against histology [37] in hearts explanted from humans at the time of heart transplantation. "
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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.
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    • "To date, ECV appears better associated with patient outcomes [20,21], compared to the partition coefficient and post contrast T1. Agreement with the collagen volume fraction appears significantly higher for ECV [24,54,63] compared to isolated post contrast T1 [70,71] which does not vary linearly with GBCA concentration. Further study of these issues would be beneficial. "
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    ABSTRACT: Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)--a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.
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