Development of advanced MRI techniques for cardiovascular research in rodent models
Lead Research Organisation:
University of Edinburgh
Department Name: Medical Radiology
Abstract
The availability of transgenic rodent (mouse and rat) models of human diseases is revolutionising preclinical research. In particular, non-invasive imaging of rodents with magnetic resonance imaging (MRI) is enabling very powerful studies using the minimum possible number of animals. In this project we are concerned with common cardiovascular diseases such as high blood pressure, diabetes and arterial disease, which are major causes of death in the Western world. Of particular interest are the function of the heart, and blood flow in the major arteries. One problem with MRI is the length of time it can take to collect the images. For example, to collect movies of how the heart pumps and the blood flows, scanning can take more than an hour with standard techniques. We will develop advanced scanning and image processing techniques to reduce the time that individual animals are in the MRI scanner. In order to develop our imaging techniques without using live animals, we will first build a rodent heart simulator that mimics the pumping action of the heart. This project directly addresses the 3R’s of biomedical research (www.nc3rs.org.uk): REDUCTION of animal numbers and scanning time, REFINEMENT of experiments, and REPLACEMENT of animals with the heart simulator for development purposes.
Technical Summary
The development of transgenic mouse models of human diseases has revolutionised biomedical research over the last few years. Coupled with the increasing availability of high-field MRI systems, powerful longitudinal studies are becoming possible with the minimum use of experimental animals. Noninvasive imaging such as MRI allows both refinement of studies and reduction in animal numbers. However, a fundamental problem with cardiovascular applications of MRI is the need to synchronise the image acquisition to the cardiac and respiratory cycles to minimise motion artefacts, and this leads to long examination times.
In this project, we will...
(i) develop simple MR-compatible ?rodent heart? and ?rodent aorta? phantoms to mimic in vivo cardiac and respiratory motion and blood flow, thereby reducing the usage of live animals for technique development;
(ii) develop methods for reducing imaging time by acquiring incomplete k-space data. We will use a retrospectively-gated ?cine? imaging sequence with variable density sampling of k-space. Ambiguities in the reconstructed images will be resolved by making use of a priori knowledge about the spatio-temporal characteristics of the signals. To date, these techniques have been applied only in human imaging. Translation to small animal cardiac imaging would be of great benefit in increasing experimental throughput and in reducing the time for which individual animals need to be anaesthetised;
(iii) address the MR-measurement of blood flow, which is well-established in clinical research, but has been largely neglected in rodent models. Flow measurements in rodent aortas are within the capabilities of modern high-field MRI systems, and will provide valuable data on cardiac output, renal blood flow and wall shear stress.
The imaging techniques will be evaluated as part of ongoing experimental studies. Measurements of left ventricular volume and function will be made in models of hypertension, obesity and myocardial infarction. Blood flow measurements will be particularly applicable to studies of renal blood flow and function, and in studies of atherosclerotic plaque development.
The applicants (imaging physicists, engineers and biologists) have extensive experience of the development and application of imaging methodology in both human and experimental animals. Most of the research will be carried out within the 5*-rated Centre for Cardiovascular Science at the University of Edinburgh. The Centre has access to a state-of-the-art high-field MRI scanner dedicated to rodent research.
In this project, we will...
(i) develop simple MR-compatible ?rodent heart? and ?rodent aorta? phantoms to mimic in vivo cardiac and respiratory motion and blood flow, thereby reducing the usage of live animals for technique development;
(ii) develop methods for reducing imaging time by acquiring incomplete k-space data. We will use a retrospectively-gated ?cine? imaging sequence with variable density sampling of k-space. Ambiguities in the reconstructed images will be resolved by making use of a priori knowledge about the spatio-temporal characteristics of the signals. To date, these techniques have been applied only in human imaging. Translation to small animal cardiac imaging would be of great benefit in increasing experimental throughput and in reducing the time for which individual animals need to be anaesthetised;
(iii) address the MR-measurement of blood flow, which is well-established in clinical research, but has been largely neglected in rodent models. Flow measurements in rodent aortas are within the capabilities of modern high-field MRI systems, and will provide valuable data on cardiac output, renal blood flow and wall shear stress.
The imaging techniques will be evaluated as part of ongoing experimental studies. Measurements of left ventricular volume and function will be made in models of hypertension, obesity and myocardial infarction. Blood flow measurements will be particularly applicable to studies of renal blood flow and function, and in studies of atherosclerotic plaque development.
The applicants (imaging physicists, engineers and biologists) have extensive experience of the development and application of imaging methodology in both human and experimental animals. Most of the research will be carried out within the 5*-rated Centre for Cardiovascular Science at the University of Edinburgh. The Centre has access to a state-of-the-art high-field MRI scanner dedicated to rodent research.