Abnormalities in the development of the cardiovascular system are among the most common congenital human birth defects. The mouse has proven to be an excellent model to study aberrant cardiovascular development, with the range of phenotypes observed in the mouse rivaling those encountered in humans. In many cases it is clear that complex phenotypes arise because impaired function causes an array of secondary defects that mask the original defect. Better tools are needed to characterize mutations that primarily affect cardiovascular function at early time points so primary defects in function are not missed. Here we will develop tools for using Optical Coherence Tomography as a routine method for studying cardiovascular abnormalities in mouse embryos. This method has a higher spatial resolution than currently used Ultrasound methods. The goal of this study is to show that OCT can be used to obtain sensitive measurements of heart function and blood flow, rivaling those that we have obtained in very early embryos using high-speed confocal microscopy. Our long term goal is to develop turn-key OCT systems for the routine phenotyping of mutant mice produced by large-scale screens.

Public Health Relevance

7. Project Narrative This proposal will develop novel technology and methods to study congenital birth defects in mouse models. Approximately 35,000 children are born each year with a congenital defect in the cardiovascular system and this is the number one cause of birth-defect related deaths. Although there has been much progress in defining genes that are required for normal cardiovascular development, we need new methods to understand how mutations in these genes cause specific alterations in cardiac and endothelial cell morphogenesis that result in birth defects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095586-04
Application #
8277099
Study Section
Microscopic Imaging Study Section (MI)
Program Officer
Buxton, Denis B
Project Start
2009-09-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$414,439
Indirect Cost
$65,321
Name
Baylor College of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Larin, Kirill V; Tuchin, Valery V; Vitkin, Alex (2014) Special section guest editorial: Optical coherence tomography and interferometry: advanced engineering and biomedical applications. J Biomed Opt 19:021101
Udan, Ryan S; Piazza, Victor G; Hsu, Chih-Wei et al. (2014) Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy. Development 141:4406-14
Wang, Shang; Larin, Kirill V (2014) Shear wave imaging optical coherence tomography (SWI-OCT) for ocular tissue biomechanics. Opt Lett 39:41-4
Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C et al. (2013) Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging. J Biomed Opt 18:20506
Bhat, Sandeep; Larina, Irina V; Larin, Kirill V et al. (2013) 4D reconstruction of the beating embryonic heart from two orthogonal sets of parallel optical coherence tomography slice-sequences. IEEE Trans Med Imaging 32:578-88
Larina, Irina V; Larin, Kirill V; Justice, Monica J et al. (2011) Optical Coherence Tomography for live imaging of mammalian development. Curr Opin Genet Dev 21:579-84
Syed, Saba H; Larin, Kirill V; Dickinson, Mary E et al. (2011) Optical coherence tomography for high-resolution imaging of mouse development in utero. J Biomed Opt 16:046004
Ohn, Jungho; Yang, Jennifer; Fraser, Scott E et al. (2011) High-speed multicolor microscopy of repeating dynamic processes. Genesis 49:514-21
Ghosn, Mohamad G; Sudheendran, Narendran; Wendt, Mark et al. (2010) Monitoring of glucose permeability in monkey skin in vivo using Optical Coherence Tomography. J Biophotonics 3:25-33
Bhat, Sandeep; Larina, Irina V; Larin, Kirill V et al. (2009) Multiple-cardiac-cycle noise reduction in dynamic optical coherence tomography of the embryonic heart and vasculature. Opt Lett 34:3704-6

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