title: Automatic quantification of the myocardial extracellular volume by cardiac computed tomography: Synthetic ECV by CCT.
abstract: BACKGROUND
  The quantification of extracellular volume fraction (ECV) by Cardiac Computed Tomography (CCT) can identify changes in the myocardial interstitium due to fibrosis or infiltration. Current methodologies require laboratory blood hematocrit (Hct) measurement - which complicates the technique. The attenuation of blood (HUblood) is known to change with anemia. We hypothesized that the relationship between Hct and HUbloodcould be calibrated to rapidly generate a synthetic ECV without formally measuring Hct.
  
  
  METHODS
  The association between Hct and HUbloodwas derived from forty non-contrast thoracic CT scans using regression analysis. Synthetic Hct was then used to calculate synthetic ECV, and in turn compared with ECV using blood Hct in a validation cohort with mild interstitial expansion due to fibrosis (aortic stenosis, n = 28, ECVCT= 28 ± 4%) and severe interstitial expansion due to amyloidosis (n = 27; ECVCT= 54 ± 11%, p < 0.001). For histological validation, synthetic ECV was correlated with collagen volume fraction (CVF) in a separate cohort with aortic stenosis (n = 18). All CT scans were performed at 120 kV and 160 mAs.
  
  
  RESULTS
  HUbloodwas a good predictor of Hct (R2= 0.47; p < 0.01), with the regression model (Hct = [0.51 * HUblood] + 17.4) describing the association. Synthetic ECV correlated well with conventional ECV (R2= 0.96; p < 0.01) with minimal bias and 2SD difference of 5.7%. Synthetic ECV correlated as well as conventional ECV with histological CVF (both R2= 0.50, p < 0.01). Finally, we implemented an automatic ECV plug-in for offline analysis.
  
  
  CONCLUSIONS
  Synthetic ECV by CCT provides instantaneous quantification of the myocardial extracellular space without the need for blood sampling.
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK; Institute of Cardiovascular Science, University College London, London, UK. Electronic address: Thomas.Treibel.12@ucl.ac.uk.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Treibel
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK; Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Fontana
authors.affiliation: Institute of Cardiovascular Science, University College London, London, UK; UCL Centre for Medical Image Computing, Department of Medical Physics, London, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Steeden
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK.
authors.forename: Arthur
authors.initials: A
authors.lastname: Nasis
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Yeung
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK; Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Steven K
authors.initials: SK
authors.lastname: White
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Sri
authors.initials: S
authors.lastname: Sivarajan
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Shonit
authors.initials: S
authors.lastname: Punwani
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pugliese
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Taylor
authors.affiliation: Barts Heart Centre, St Bartholomew's Hospital, London, UK; Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Bandula
mesh_terms: D000686:Amyloidosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D001331:Automation; D009202:Cardiomyopathies / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D005355:Fibrosis; D006400:Hematocrit; D006801:Humans; D061330:Multidetector Computed Tomography / Q000379:methods*; D009206:Myocardium / Q000473:pathology*; D015588:Observer Variation; D011237:Predictive Value of Tests; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies
keywords: Cardiac amyloidosis; Computed tomography; Extracellular matrix; Myocardial extracellular volume fraction; Myocardial fibrosis; Myocardial tissue characterization