Abstract

Purpose:In vivo imaging of the pulmonary vasculature in small animals is difficult yet highly desirable in order to allow study of the effects of a host of dynamic biological processes such as hypoxic pulmonary vasoconstriction. Here the authors present an approach for the quantification of changes in the vasculature.Methods:A contrast free angiography technique is validated in silico through the use of computer-generated images and in vivo through microcomputed tomography (μCT) of live mice conducted using a laboratory-based x-ray source. Subsequent image processing on μCT data allowed for the quantification of the caliber of pulmonary vasculature without the need for external contrast agents. These measures were validated by comparing with quantitative contrast microangiography in the same mice.Results:Quantification of arterial diameters from the method proposed in this study is validated against laboratory-based x-ray contrast microangiography. The authors find that there is a high degree of correlation (R = 0.91) between measures from microangiography and their contrast free method.Conclusions:A technique for quantification of murine pulmonary vasculature without the need for contrast is presented. As such, this technique could be applied for longitudinal studies of animals to study changes to vasculature without the risk of premature death in sensitive mouse models of disease. This approach may also be of value in the clinical setting.

Highlights

  • Diseases of the lungs often involve derangements of complex physiological processes that cannot be effectively studied in vitro or in postmortem samples

  • A contrast free angiography technique is validated in silico through the use of computergenerated images and in vivo through microcomputed tomography of live mice conducted using a laboratory-based x-ray source

  • Other techniques that have been used to quantify the distribution of pulmonary blood flow in small animals include injection of fluorescent microspheres and postmortem histological quantification,3 microcomputed tomography imaging of the lungs with contrast agents either in vivo4 or after radiopaque silicone polymer injection followed by ex vivo lung imaging,5 and microangiography in mice using synchrotron radiation

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Summary

Introduction

Diseases of the lungs often involve derangements of complex physiological processes that cannot be effectively studied in vitro or in postmortem samples. Other techniques that have been used to quantify the distribution of pulmonary blood flow in small animals include injection of fluorescent microspheres and postmortem histological quantification, microcomputed tomography (μCT) imaging of the lungs with contrast agents either in vivo or after radiopaque silicone polymer injection followed by ex vivo lung imaging, and microangiography in mice using synchrotron radiation.. Other techniques that have been used to quantify the distribution of pulmonary blood flow in small animals include injection of fluorescent microspheres and postmortem histological quantification, microcomputed tomography (μCT) imaging of the lungs with contrast agents either in vivo or after radiopaque silicone polymer injection followed by ex vivo lung imaging, and microangiography in mice using synchrotron radiation.6 Most of these methods preclude repeated imaging due to the terminal nature of the imaging procedures and.

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