title: Quantification of extracellular matrix expansion by CMR in infiltrative heart disease.
abstract: OBJECTIVE
  The aim of this study was to perform direct quantification of myocardial extracellular volume fraction (ECF) with T1-weighted cardiac magnetic resonance (CMR) imaging in patients suspected to have infiltrative heart disease.
  
  
  BACKGROUND
  Infiltrative heart disease refers to accumulation of abnormal substances within the myocardium. Qualitative assessment of late gadolinium enhancement (LGE) remains the most commonly used method for CMR evaluation of patients suspected with myocardial infiltration. This technique is widely available and can be performed in a reproducible and standardized manner. However, the degree of extracellular matrix expansion due to myocardial infiltration in the intercellular space has, to date, not been amenable to noninvasive quantification with LGE.
  
  
  METHODS
  We performed 3-T CMR in 38 patients (mean age 68 ± 15 years) who were referred for assessment of infiltrative heart disease and also in 9 healthy volunteers as control subjects. The T1 quantification by Look-Locker gradient-echo before and after contrast determined segmental myocardial partition coefficients. The ECF was obtained by referencing the tissue partition coefficient for gadolinium to the plasma volume fraction in blood, derived from serum hematocrit. Cine CMR and LGE imaging in matching locations were also performed.
  
  
  RESULTS
  Seventeen patients (45%) had cardiac amyloidosis (CA) (biopsy-confirmed or clinically highly probable), 20 (53%) had a non-amyloid cardiomyopathy, and 1 had lysosomal storage disease. Median global ECF was substantially higher in CA patients (0.49) compared with non-amyloid cardiomyopathy patients (0.33, p < 0.0001) and volunteers (0.24, p = 0.0001). The ECF strongly correlated with visually assessed segmental LGE (r = 0.80, p < 0.0001) and LV mass index (r = 0.69, p < 0.0001), reflecting severity of myocardial infiltration. In patients with CA, ECF was highest in segments with LGE, although it remained elevated in segments without qualitative LGE.
  
  
  CONCLUSIONS
  The CMR ECF quantification identified substantial expansion of the interstitial space in patients with CA compared with volunteers. Further studies using this technique for diagnosis and assessment of the severity of myocardial infiltration are warranted.
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: François-Pierre
authors.initials: FP
authors.lastname: Mongeon
authors.forename: Michael
authors.initials: M
authors.lastname: Jerosch-Herold
authors.forename: Otávio Rizzi
authors.initials: OR
authors.lastname: Coelho-Filho
authors.forename: Ron
authors.initials: R
authors.lastname: Blankstein
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Falk
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Kwong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000473:pathology; D001706:Biopsy; D009202:Cardiomyopathies / Q000473:pathology*; D016009:Chi-Square Distribution; D003287:Contrast Media; D003430:Cross-Sectional Studies; D005109:Extracellular Matrix / Q000473:pathology*; D019786:Gadolinium DTPA; D006801:Humans; D016014:Linear Models; D016464:Lysosomal Storage Diseases / Q000473:pathology; D019028:Magnetic Resonance Imaging, Cine; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA