Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology

Abstract

Aims: 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.

Methods and results: 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).

Conclusion: 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.

Figures

Figure 1

A flow chart describing the process of generating a composite quantitative extracellular volume fraction (ECV) image of a mid-ventricular short-axis slice through the left ventricle. The top row shows two quantitative T1 maps generated from Modified Look-Locker Inversion-recovery images acquired 15 min after (Post-Gd) and before (Pre-Gd) administration of a gadolinium (Gd)-based extracellular contrast agent. Both T1 maps are displayed with the same grey scale. The reciprocal of each pixel value is taken to generate R1 maps (bottom-left two images labelled R1). The Pre-Gd R1 map pixel values are subtracted from the Post-Gd R1 map to generate a ΔR1 map. The R1 maps and the ΔR1 map are all displayed with the same grey scale. In the ΔR1 map, the ΔR1 value of the left ventricular blood pool is measured in a region of interest (black oval). The ΔR1 map pixel values are then multiplied by one minus the haematocrit (hct) and divided by the mean of ΔR1 value of the blood pool (ΔR1blood) in order to get the composite extracellular volume fraction image, ranging in values between 0 and 100%. See Supplementary material online for details regarding the theoretical background behind the operations.

Figure 2

Late gadolinium enhancement (left) and quantitative extracellular volume fraction images (right) in a patient with prior myocardial infarction (Infarct) in the lateral wall (arrowheads), a patient with hypertrophic cardiomyopathy associated with atypical enhancement (Atypical) in the septum (arrowheads), and a patient with normal late gadolinium enhancement findings (Normal). Differences in extracellular volume fraction in the blood pool are attributable to differences in haematocrit. In the patient with a lateral infarct, most of the septum appears normal except a small patch of late gadolinium enhancement in the basal septum. The colour scale ranges from 0 to 100% extracellular volume. The normal range (mean ± 2 SD) of ‘normal appearing’ myocardium in our normal population is indicated in the colour scale (20–32%).

Figure 3

Extracellular volume fraction of infarcted myocardium (Infarct LGE) and regions of Atypical LGE were significantly higher than ‘normal appearing’ myocardium.

Figure 4

Extracellular volume fraction of myocardium increases as a function of age. Directionally, these findings are consistent with an age-related increase in diffuse fibrosis.

Figure 5

Extracellular volume fraction of ‘normal appearing’ myocardium is inversely related to ejection fraction in patients with myocardial infarction. These findings are consistent with adverse post-infarct remodelling in myocardium remote from infarction.

Figure 6

The relationship between T1, R1, ΔR1, and extracellular volume fraction of normal myocardium (black squares) and blood (white circles) over time after contrast injection in healthy volunteers (n = 11). R1 is equal to 1/T1. ΔR1 is the difference between post-contrast and pre-contrast R1. ΔR1 is proportional to contrast agent concentration. Extracellular volume fraction is the extracellular volume fraction and is defined as the ratio of ΔR1 of the myocardium to ΔR1 of the blood, multiplied by one minus haematocrit. See Methods and Supplementary material online for details. Extracellular volume fraction effectively remains constant over the time period after contrast injection, indicating that the relationship between contrast agent concentration in the myocardium and in the blood is in a dynamic equilibrium. Extracellular volume fraction measurement in normal myocardium inherently compensates for renal clearance and is thus not dependent on imaging time after contrast injection. Statistical differences by analysis of variance with Bonferroni correction are denoted according to the convention: ***P < 0.001, **P < 0.01, and *P < 0.05.