Myocardial Extracellular Volume Fraction From T1 Measurements in Healthy Volunteers and Mice: Relationship to Aging and Cardiac Dimensions

Abstract

This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. In healthy volunteers (N= 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r= 0.74, p < 0.001), maximal left atrial volume index (r= 0.67, p < 0.001), and indexed left ventricular mass. There were no differences in the ECV between segments in a slice or between slices. In mice (N= 12), the myocardial ECV ranged from 0.20 to 0.32 and increased with age (0.22 ± 0.02 vs. 0.30 ± 0.02, juvenile vs. aged mice, p < 0.001). In mice, the ECV correlated with the extent of myocardial fibrosis (r= 0.94, p < 0.001). In healthy volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis.