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

• DOI: 10.1161/circimaging.112.000192
• Publication Date: 2013-04-04T06:34:21Z
• Authors: Christopher A. Mi...; Josephine H. Naish; Paul Bishop; Glyn Coutts; David Clark; Sha Zhao; Simon G. Ray; Nizar Yonan; Simon G. Williams; Andrew S. Flett; James C. Moon; Andreas Greiser; Geoffrey J.M. Parker; Matthias Schmitt
• Keywords: Adult; Gadolinium DTPA; Male; Heart Diseases; Histopathology; Contrast Media; 03 medical and health sciences; 0302 clinical medicine; Myocardial fibrosis; Humans; Coloring Agents; Aged; Analysis of Variance; Middle Aged; Fibrosis; Magnetic Resonance Imaging; 3. Good health; Extracellular Matrix; Hematocrit; Linear Models; Heart Transplantation; Female; Collagen; Azo Compounds; Biomarkers; MRI

Background—

Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T 1 -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 T 1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T 1 , used as an ECV surrogate.

Methods and Results—

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 T 1 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 T 1 ). Correlation was maintained throughout the entire heart. Isolated postcontrast T 1 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 T 1 ), but between-subject correlations were not significant. DynEq-CMR–derived ECV varied significantly according to contrast dose, myocardial region, and sex.

Conclusions—

DynEq-CMR–derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T 1 measurement is insufficient for ECV assessment.