Point estimate and reference normality interval of MRI-derived myocardial extracellular volume in healthy subjects: a systematic review and meta-analysis

OBJECTIVES: To estimate the MRI-derived myocardial extracellular volume (ECV) in healthy subjects together with reference normality interval. METHODS: The study was registered on PROSPERO and reported according to PRISMA. In October 2017, a systematic search (MEDLINE/EMBASE) was performed for articles reporting MRI-derived ECV in healthy subjects. The pooled ECV (pECV) with 95% confidence interval (CI) was calculated using the random-effect model; the normality interval was calculated as pECV ± 2 root mean square of all study standard deviations. The Newcastle-Ottawa scale was used for assessing study quality, subgroup/meta-regression analyses for technical/biological covariates, and Egger test for publication bias risk. RESULTS: Of 282 articles, 56 were analyzed totaling 1851 subjects with age 16-68 years, body mass index 23-28 kg/m2, and left ventricular ejection fraction 58-74%. Contrast dose varied from 0.075 to 0.200 mmol/kg. Heterogeneity was high (I2 = 92%). The pECV was 25.6% (95% CI 25.2-26.0%) with a normality interval of 19.6-31.6%. pECV was slightly increasing with age (β = 0.03%, p = 0.038) and slightly decreasing with the percentage of males (β = - 0.02%, p = 0.053). Sequence type significantly (p = 0.003) impacted on pECV: the normal interval was 19.9-31.9% for MOLLI and 20.3-33.5% for ShMOLLI. Contrast type/dose, time of acquisition, and magnetic field strength did not significantly impact pECV (p > 0.093). Quality was moderate or high in 48/56 studies (86%). No risk of publication bias (p = 0.728). CONCLUSIONS: Myocardial pECV in healthy subjects was 25.6%, increasing by 0.03% for each year of age. The ECV normality interval was 19.9-31.9% for MOLLI and 20.3-33.5% for ShMOLLI. KEY POINTS: • The pooled estimate of normal MRI-derived ECV based on 1851 subjects was 25.6%, slightly increasing with age and slightly decreasing with the percentage of males. • MRI-derived ECV was independent of contrast type/dose and field strength but dependent on the imaging sequence. • The modeled normality reference interval of MRI-derived ECV was 19.9-31.9% for the MOLLI sequence and 20.3-33.5% for the ShMOLLI sequence.