European Radiology

, Volume 29, Issue 12, pp 6620–6633 | Cite as

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

  • Francesco Sardanelli
  • Simone Schiaffino
  • Moreno ZanardoEmail author
  • Francesco Secchi
  • Paola Maria Cannaò
  • Federico Ambrogi
  • Giovanni Di Leo
Magnetic Resonance



To estimate the MRI-derived myocardial extracellular volume (ECV) in healthy subjects together with reference normality interval.


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.


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).


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.


Magnetic resonance imaging Meta-analysis Fibrosis Cardiomyopathies Biomarkers 



Confidence interval


Extracellular volume


Late gadolinium enhancement


Modified Look-Locker inversion recovery


Magnetic resonance imaging


Preferred Reporting Items for Systematic Reviews and Meta-analyses


Standard deviation


Shortened modified Look-Locker inversion recovery



This study was supported by local research funds of the IRCCS Policlinico San Donato, a Clinical Research Hospital partially funded by the Italian Ministry of Health.


The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Prof. Francesco Sardanelli.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Francesco Sardanelli declares to have received grants from or being a member of speakers’ bureau/advisory board for Bayer, Bracco, and General Electric. Francesco Secchi and Giovanni Di Leo have been sponsored to congresses by Bracco Imaging SpA (Milan, Italy). Simone Schiaffino declares to have received grants from or being a member of speakers’ bureau for General Electric.

Statistics and biometry

Federico Ambrogi provided statistical advice for this manuscript. Federico Ambrogi has significant statistical expertise.

Informed consent

Written informed consent was not required for this study because the article type is a systematic review with meta-analysis.

Ethical approval

Institutional Review Board approval was not required because the article type is a systematic review with meta-analysis.


• Prospective

• Performed at one institution

Supplementary material

330_2019_6185_MOESM1_ESM.docx (267 kb)
ESM 1 Fig. S1. Funnel plot showing no risk of publication bias, confirmed by the Egger test (p = 0.728). Fig. S2. Forest plot of the subgroup analysis using the magnetic field strength as inter-study factor. Heterogeneity among studies was very high (I2 ≥ 94%). The difference in extracellular volume between 1.5 T and 3 T was not significant (p = 0.896). Fig. S3. Forest plot of the subgroup analysis using the type of contrast agent as inter-study factor. Heterogeneity among studies was from moderate to very high (I2 52%–97%). The difference in extracellular volume among contrast agents was not significant (p = 0.759). Fig. S4. Forest plot of the subgroup analysis using the magnetic resonance sequence as inter-study factor. Heterogeneity among studies was very high (I2 82%–87%). The difference in extracellular volume among sequences was significant (p = 0.003). (DOCX 267 kb)


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Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  1. 1.Radiology UnitIRCCS Policlinico San DonatoMilanItaly
  2. 2.Department of Biomedical Sciences for HealthUniversità degli Studi di MilanoMilanItaly
  3. 3.PhD Course in Integrative Biomedical ResearchUniversità degli Studi di MilanoMilanItaly
  4. 4.Department of Clinical Sciences and Community HealthUniversità degli Studi di MilanoMilanItaly

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