Feasibility of replacing invasive heart pressure measurements with non-invasive MR Elastography to reduce rodent numbers in pre-clinical research

Lead Research Organisation: University of Oxford
Department Name: RDM Cardiovascular Medicine

Abstract

Magnetic resonance imaging (MRI) is a technique used to investigate size, structure and function of the heart. However, conventional MRI does not provide information on the pressure that the heart muscle must generate in order to pump blood through the body. This pressure is a fundamental parameter of cardiac function and can currently only be determined by inserting a catheter directly into the heart. Particularly in mice and rats, which are the predominant animal species used in cardiovascular research, this is an invasive and technically very challenging procedure that can be performed only once. We therefore propose to investigate whether or not a novel MR technique can overcome this limitation, and can be used to measure the pressure in the heart of mice and rats without inserting a catheter into the animal. If successful, this method will represent a valuable tool for scientists studying progression and treatment of heart disease, but most importantly it will reduce the numbers of animals required for this type of research by obviating the need to kill animals simply to obtain basic cardiac pressure measurements.

Technical Summary

Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) are sophisticated phenotyping techniques that allow for a non-invasive characterization of cardiac function, anatomy, structure and metabolism in rodents. However, when assessing myocardial function the isovolumic phases of the cardiac cycle are not directly accessible to imaging techniques, yet this is where maximal rates of pressure generation and relaxation occur. This type of information is only available using LV catheterization, which in rodents is an invasive and terminal procedure, requiring new experimental groups for every time-point. Magnetic Resonance Elastography (MRE), which measures shear deformation following mechanical tissue stimulation, has the potential to non-invasively assess ventricular pressure in vivo, as successfully demonstrated in pig and in human hearts. However, this technique has not yet been applied to rodent hearts. We hypothesize that MRE can also be used to non-invasively measure left-ventricular pressure-volume curves with sufficient temporal resolution to detect subtle phenotypes in surgically and genetically manipulated rodents. We therefore propose to conduct a pilot study with the aim to develop the tools, which will be necessary to investigate this hypothesis. If successful, MRE will have the potential to replace the invasive and terminal hemodynamic procedure in basic cardiovascular research, leading to a reduction in animal usage.

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