Melissa A Krueger1, Sabine S Huke, Robb W Glenny. 1. Division of Pulmonary and Critical Care Medicine, Box 356522, University of Washington School of Medicine, Seattle, WA 98195, USA. krueger@uw.edu
Abstract
RATIONALE: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information. OBJECTIVE: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice. METHODS AND RESULTS: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice. CONCLUSIONS: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.
RATIONALE: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information. OBJECTIVE: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice. METHODS AND RESULTS: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice. CONCLUSIONS: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.
Authors: Etienne Croteau; Jennifer M Renaud; Matthew McDonald; Ran Klein; Jean N DaSilva; Rob S B Beanlands; Robert A deKemp Journal: Eur J Nucl Med Mol Imaging Date: 2015-07-05 Impact factor: 9.236
Authors: Matthew Sinclair; Jack Lee; Andreas Schuster; Amedeo Chiribiri; Jeroen van den Wijngaard; Pepijn van Horssen; Maria Siebes; Jos A E Spaan; Eike Nagel; Nicolas P Smith Journal: Microvasc Res Date: 2015-05-09 Impact factor: 3.514
Authors: Patiwet Wuttisarnwattana; Madhusudhana Gargesha; Wouter van't Hof; Kenneth R Cooke; David L Wilson Journal: IEEE Trans Med Imaging Date: 2015-11-02 Impact factor: 10.048