Mouse Cardiac Imaging Using UBM YuQing Zhou Mouse Imaging Centre, The Hospital for Sick Children, To

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Mouse Cardiac Imaging Using UBMYu-Qing
ZhouMouse Imaging Centre, The Hospital for Sick
Children, Toronto
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Background

• Genetically engineered mice have been generated
  to model human cardiovascular diseases.
• Ultrasound biomicroscopy (UBM) provides great
  tool for small animal imaging
• High spatial resolution 50 µm
• Morphology, function and hemodynamics
• Noninvasive for serial observations
• Combination of these two aspects opens a
  promising field in biological research
  constitutes an important component of molecular
  imaging.

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(A) Embryonic cardiac imaging
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E8.5 day - the first day the embryonic heart
starts to pump
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E9.5 day - a U-shaped primitive heart tube
flow
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Embryonic cardiac morphology at the following
gestational days
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Abnormal aortic valve formation flow
regurgitation
Wild-type NFATc1-/-
Phoon C, et al. Circ Res 95(1)92-99, 2004
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• Difficulties in trans-abdominal imaging
• Embryonic tagging
• Embryonic orientation location
• Relative movement embryonic maternal
  respiration
• Relative size of Doppler sample volume

Solutions Exteriorizing the uterus using
higher frequency (55MHz)
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(B) Postnatal cardiac imaging
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Phenotyping the mutant mouse models of human
cardiac diseases
Human Holt-Oram Syndrome

• Tbx5del/ mouse model
• Cardiac defects
• ASD and/or VSD conduction disturbances
• Limb abnormalities
• In vivo cardiac function hemodynamics unknown

Bensen DW et al. Circulation 972043-481998
Yang JF et al. Am J Med Genet 92237-240 2000
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2.10.3 mm (n11) vs 3.61.0 mm (n10)
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Wild-type Tbx5del/
MO
PV
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Developmental change of mitral flow pattern in
Tbx5del/ mice (n12)
Wild-type
Tbx5del/
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ASD bi-directional flow through the
shunt Tbx5del/ neonate, 2 wks old
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MRI cardiac anatomical confirmation
Wild-type 8 wks Tbx5del/
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(C) Imaging of transplanted heart
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Heterotopic cardiac transplantation
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Aortic regurgitation
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Mitral regurgitation
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Doppler flow of the coronary artery
Native heart Transplanted heart
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(D) Other vasculatures
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Renal artery and vein
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Acknowledgements
MICe colleagues, especially, F. Stuart
Foster R. Mark Henkelman Lorinda Davidson Jun
Dazai Jonathan Bishop Ultrasound group at
Sunnybrook
Benoit Bruneau Yonghong Zhu Lori West Rami
Bishay Fraser Golding S. Lee Adamson VisualSonic
s Inc.

• Financial supports
• Canada Foundation for Innovation (CFI)
• Ontario Innovation Trust (OIT)
• Ontario Research and Development Challenge Fund
  (ORDCF) grant to the Ontario Consortium for Small
  Animal Imaging (OCSAI)