Extracellular volume fraction mapping in the myocardium, part 2: initial clinical experience

Abstract

Background: Diffuse myocardial fibrosis, and to a lesser extent global myocardial edema, are important processes in heart disease which are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial extracellular volume fraction (ECV) circumvents factors that confound T1-weighted images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV would be clinically useful for detecting both focal and diffuse myocardial abnormalities in a variety of common and uncommon heart diseases.

Methods: A total of 156 subjects were imaged including 62 with normal findings, 33 patients with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally-elevated ECV was defined as >2SD from the mean ECV in individuals with normal findings. In HCM the size of regions of LGE was quantified as the region >2 SD from remote.

Results: Mean ECV of 62 normal individuals was 25.4 ± 2.5% (m ± SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial infarctions (without MVO) (N=33) measured 68.5 ± 8.6% (p<0.001 vs normal). In HCM, the extent of abnormally elevated ECV correlated to the extent of LGE (r=0.72, p<0.001) but had a systematically greater extent by ECV (mean difference 19 ± 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients with non-ischemic DCM (38.1 ± 1.9% (p<0.001 vs normal) and LGE in the same slice appeared "normal" in 2 of these 4 patients. Mean ECV values in other disease entities ranged 32-60% for cardiac amyloidosis (N=4), 40-41% for systemic capillary leak syndrome (N=2), and 39-56% within abnormal regions affected by myocarditis (N=7).

Conclusions: ECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse disease. The ability to display ECV maps in units that are physiologically intuitive and may be interpreted on an absolute scale offers the potential for detection of diffuse disease and measurement of the extent and severity of abnormal regions.

Figures

Figure 1

ECV values for normal myocardium (n = 62), focal abnormalities in HCM (n = 33), and chronic MI (n = 33). Box and whisker plots show median, 25 and 75 percentiles, and range.

Figure 2

LGE and corresponding ECV map for subject with HCM. LGE values > mean + 2SD measured in a “normal” region and ECV values > 30.4% fixed threshold (corresponding to the mean + 2SD for myocardium in a normal group) are classified as abnormal.

Figure 3

Comparison of the percent of myocardium classified as abnormal by ECV using a fixed threshold (ECV > 30.4%) and the percent of LGE > mean + 2SD (measured in remote “normal”). Linear fit (red) is%ECV = 1.07%LGE = 0.19.

Figure 4

Examples illustrating excellent agreement between LGE and ECV in cases of focal abnormalities in myocardial ECV. Pre-contrast T1-maps (top row), post-contrast T1-maps (2nd row), late gadolinium enhancement (3rd row), and ECV maps (bottom row) for patients with: (a) chronic MI, (b) acute myocarditis, and (c) HCM.

Figure 5

Examples illustrating cases with diffuse abnormalities in myocardial ECV which are challenging to assess with conventional LGE. Pre-contrast T1-maps (top row), post-contrast T1-maps (2nd row), late gadolinium enhancement (3rd row), and ECV maps (bottom row) for patients with various cardiomyopathies: (a) non-ischemic DCM with diffusely elevated ECV and normal appearing LGE, (b) cardiac amyloidosis with “patchy” LGE enhancement, (c) cardiac amyloidosis with diffusely elevated ECV and globally nulled LGE, and (d) systemic capillary leak syndrome (SCLS) with globally elevated ECV due to edema and normal LGE.