Quantitative 3-dimensional echocardiography for accurate and rapid cardiac phenotype characterization in mice

Dana Dawson, Craig A Lygate, James Saunders, Jürgen E Schneider, Xujiong Ye, Karen Hulbert, J. Alison Noble, Stefan Neubauer

Research output: Contribution to journalArticle

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Abstract

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-mum 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.
Original languageEnglish
Pages (from-to)1632-1637
Number of pages6
JournalCirculation
Volume110
Issue number12
DOIs
Publication statusPublished - 21 Sep 2004

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Echocardiography
Phenotype
Stroke Volume
Magnetic Resonance Imaging
Cardiac Volume
Motion Pictures
Transducers
Histology
Electrocardiography
Heart Failure

Keywords

  • animals
  • animal disease models
  • three-dimensional echocardiography
  • heart ventricles
  • magnetic resonance imaging
  • male
  • mice
  • mice, inbred C57BL
  • myocardial infarction
  • organ size
  • phenotype
  • reproducibility of results
  • stroke volume
  • left ventricle mass
  • two-dimensional echocardiography
  • mouse model
  • rat hearts
  • quantification
  • cardiomyopathy
  • validation
  • system
  • in-vivo assessment

Cite this

Quantitative 3-dimensional echocardiography for accurate and rapid cardiac phenotype characterization in mice. / Dawson, Dana; Lygate, Craig A; Saunders, James; Schneider, Jürgen E; Ye, Xujiong; Hulbert, Karen; Noble, J. Alison; Neubauer, Stefan.

In: Circulation, Vol. 110, No. 12, 21.09.2004, p. 1632-1637.

Research output: Contribution to journalArticle

Dawson, D, Lygate, CA, Saunders, J, Schneider, JE, Ye, X, Hulbert, K, Noble, JA & Neubauer, S 2004, 'Quantitative 3-dimensional echocardiography for accurate and rapid cardiac phenotype characterization in mice', Circulation, vol. 110, no. 12, pp. 1632-1637. https://doi.org/10.1161/01.CIR.0000142049.14227.AD
Dawson, Dana ; Lygate, Craig A ; Saunders, James ; Schneider, Jürgen E ; Ye, Xujiong ; Hulbert, Karen ; Noble, J. Alison ; Neubauer, Stefan. / Quantitative 3-dimensional echocardiography for accurate and rapid cardiac phenotype characterization in mice. In: Circulation. 2004 ; Vol. 110, No. 12. pp. 1632-1637.
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AU - Saunders, James

AU - Schneider, Jürgen E

AU - Ye, Xujiong

AU - Hulbert, Karen

AU - Noble, J. Alison

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N2 - 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-mum 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.

AB - 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-mum 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.

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KW - organ size

KW - phenotype

KW - reproducibility of results

KW - stroke volume

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KW - mouse model

KW - rat hearts

KW - quantification

KW - cardiomyopathy

KW - validation

KW - system

KW - in-vivo assessment

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