title: Quantitative 3-dimensional echocardiography for accurate and rapid cardiac phenotype characterization in mice.
abstract: BACKGROUND
  Insufficient techniques exist for rapid and reliable phenotype characterization of genetically manipulated mouse models of cardiac dysfunction. We developed a new, robust, 3-dimensional echocardiography (3D-echo) technique and hypothesized that this 3D-echo technique is as accurate as magnetic resonance imaging (MRI) and histology for assessment of left ventricular (LV) volume, ejection fraction, mass, and infarct size in normal and chronically infarcted mice.
  
  
  RESULTS
  Using a high-frequency, 7/15-MHz, linear-array ultrasound transducer, we acquired ECG and respiratory-gated, 500-microm consecutive short-axis slices of the murine heart within 4 minutes. The short-axis movies were reassembled off-line in a 3D matrix by using the measured platform locations to position each slice in 3D. Epicardial and endocardial heart contours were manually traced, and a B-spline surface was fitted to the delineated image curves to reconstruct the heart volumes. Excellent correlations were obtained between 3D-echo and MRI for LV end-systolic volumes (r=0.99, P<0.0001), LV end-diastolic volumes (r=0.99, P<0.0001), ejection fraction (r=0.99, P<0.0001), LV mass (r=0.94, P<0.0019), and infarct size (r=0.98, P<0.0001). Also, excellent correlations were found between the 3D-echo-derived LV mass and necropsy LV mass in normal mice (r=0.99, P<0.0001), as well as for 3D-echo-derived infarct size and histologically determined infarct size (r=0.99, P<0.0001) in mice with chronic heart failure. Bland-Altman analysis showed excellent limits of agreement between techniques for all measured parameters.
  
  
  CONCLUSIONS
  This new, fast, and highly reproducible 3D-echo technique should be of widespread applicability for high-throughput murine cardiac phenotyping studies.
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, Oxford, England.
authors.forename: Dana
authors.initials: D
authors.lastname: Dawson
authors.forename: Craig A
authors.initials: CA
authors.lastname: Lygate
authors.forename: James
authors.initials: J
authors.lastname: Saunders
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
authors.forename: Xujiong
authors.initials: X
authors.lastname: Ye
authors.forename: Karen
authors.initials: K
authors.lastname: Hulbert
authors.forename: J Alison
authors.initials: JA
authors.lastname: Noble
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019560:Echocardiography, Three-Dimensional / Q000662:veterinary*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D010641:Phenotype; D015203:Reproducibility of Results; D013318:Stroke Volume