Published Online
on September 13, 2004

A more recent version of this article appeared on September 21, 2004

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Submitted on December 8, 2003
Revised on April 6, 2004
Accepted on April 20, 2004

Quantitative 3-Dimensional Echocardiography for Accurate and Rapid Cardiac Phenotype Characterization in Mice

Dana Dawson MBBS, MRCP, Craig A. Lygate MRPharmS, PhD, James Saunders BSc, Jürgen E. Schneider PhD, Xujiong Ye PhD, Karen Hulbert BSc, J. Alison Noble PhD, FIEE, and Stefan Neubauer MD, FRCP^*

From the Departments of Cardiovascular Medicine (D.D., C.A.G., J.E.S., K.H., S.N.) and Engineering Science (J.S., X.Y., J.A.N.), University of Oxford, Oxford, England.

^* To whom correspondence should be addressed. E-mail: stefan.neubauer{at}cardiov.ox.ac.uk.

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.

Methods and Results--Using a high-frequency, 7/15-MHz, linear-array ultrasound transducer, we acquired ECG and respiratory-gated, 500-µm 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.

Conclusion--This new, fast, and highly reproducible 3D-echo technique should be of widespread applicability for high-throughput murine cardiac phenotyping studies.

Key words: echocardiography • magnetic resonance imaging • mice • myocardial infarction

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