title: Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume.
abstract: BACKGROUND
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: North West Heart Centre and The Transplant Centre, University Hospitalof South Manchester, Wythenshawe Hospital, Manchester, United Kingdom. chrismiller@doctors.org.uk
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Miller
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Naish
authors.forename: Paul
authors.initials: P
authors.lastname: Bishop
authors.forename: Glyn
authors.initials: G
authors.lastname: Coutts
authors.forename: David
authors.initials: D
authors.lastname: Clark
authors.forename: Sha
authors.initials: S
authors.lastname: Zhao
authors.forename: Simon G
authors.initials: SG
authors.lastname: Ray
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.forename: Simon G
authors.initials: SG
authors.lastname: Williams
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Flett
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiser
authors.forename: Geoffrey J M
authors.initials: GJ
authors.lastname: Parker
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001391:Azo Compounds; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004396:Coloring Agents; D003287:Contrast Media; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D019786:Gadolinium DTPA; D006331:Heart Diseases / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016027:Heart Transplantation; D006400:Hematocrit; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013194:Staining and Labeling / Q000379:methods; D020257:Ventricular Remodeling; D055815:Young Adult
chemical_list: D001391:Azo Compounds; D015415:Biomarkers; D004396:Coloring Agents; D003287:Contrast Media; C009798:C.I. direct red 80; D003094:Collagen; D019786:Gadolinium DTPA
keywords: MRI; collagen; histopathology; myocardial fibrosis