Comprehensive Validation of Cardiovascular Magnetic Resonance Techniques for the Assessment of Myocardial Extracellular Volume

• Published in: Circulation. Cardiovascular imaging Vol. 6; no. 3; pp. 373 - 383
• Main Authors: Miller, Christopher A., Naish, Josephine H., Bishop, Paul, Coutts, Glyn, Clark, David, Zhao, Sha, Ray, Simon G., Yonan, Nizar, Williams, Simon G., Flett, Andrew S., Moon, James C., Greiser, Andreas, Parker, Geoffrey J.M., Schmitt, Matthias
• Format: Journal Article
• Language: English
• Published: United States 01.05.2013
• Subjects: Adult; Aged; Analysis of Variance; Azo Compounds; Biomarkers - metabolism; Collagen - metabolism; Coloring Agents; Contrast Media; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; Fibrosis; Gadolinium DTPA; Heart Diseases - blood; Heart Diseases - diagnosis; Heart Diseases - metabolism; Heart Diseases - pathology; Heart Diseases - surgery; Heart Transplantation; Hematocrit; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium - metabolism; Myocardium - pathology; Observer Variation; Predictive Value of Tests; Reproducibility of Results; Staining and Labeling - methods; Ventricular Remodeling; Young Adult; collagen; histopathology; MRI; myocardial fibrosis
• ISSN: 1941-9651; 1942-0080; 1942-0080
• DOI: 10.1161/CIRCIMAGING.112.000192

Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T1-mapping techniques are increasingly used to evaluate myocardial extracellular volume (ECV); however, the most widely applied methods are without histological validation. Our aim was to perform comprehensive validation of (1) dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit-adjusted myocardial and blood T1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T1, used as an ECV surrogate. Whole-heart histological validation was performed using 96 tissue samples, analyzed for picrosirius red collagen volume fraction, obtained from each of 16 segments of the explanted hearts of 6 patients undergoing heart transplantation who had prospectively undergone CMR before transplantation (median interval between CMR and transplantation, 29 days). DynEq-CMR-derived ECV was calculated from T1 measurements made using a modified Look-Locker inversion recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a strong linear relationship between DynEq-CMR-derived ECV and histological collagen volume fraction (P<0.001; within-subject: r=0.745; P<0.001; r(2)=0.555 and between-subject: r=0.945; P<0.01; r(2)=0.893; for ECV calculated using 15-minute postcontrast T1). Correlation was maintained throughout the entire heart. Isolated postcontrast T1 measurement showed significant within-subject correlation with histological collagen volume fraction (r=-0.741; P<0.001; r(2)=0.550 for 15-minute postcontrast T1), but between-subject correlations were not significant. DynEq-CMR-derived ECV varied significantly according to contrast dose, myocardial region, and sex. DynEq-CMR-derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T1 measurement is insufficient for ECV assessment.