Functional and molecular MR imaging of small laboratory animals

This proposal requests support for the purchase of an advanced Magnetic Resonance imaging (MRI) and spectroscopy (MRS) console for the 6.3 Tesla experimental MR scanner at Eindhoven University of Technology. The current console is outdated and is not able to support the demanding MR experiments that are needed to realize our research plans. The scanner is installed in the Department of Biomedical Engineering that is a collaboration between the universities of Eindhoven and Maastricht. The instrumentation is made available to other research groups, both within the two partner universities and elsewhere. The 6.3 Tesla MR system is primarily used for in vivo studies on mouse and rat models of human disorders. One line of research focuses on mouse models of cardiovascular diseases, which reach epidemic proportions and pose an increasing burden upon society. This fuels the need for strategies to prevent or treat these diseases. This part of our research program is dedicated to the monitoring of atherosclerosis and myocardial injury with a combination of structural and functional MRI techniques. High-resolution, multi-parametric MRI will be employed to determine the location, the size and the composition of the vascular lesions in the atherosclerosis models as a function of time. Similarly, a combination of MRI methods will be used to measure the global and local function of the mouse heart as well as the location and severity of the infarct in focal ischemia models. Apart from this more traditional MRI approach to tissue (dys)function, we have recently initiated a research program, in which we are going to monitor disease progression with MRI at the molecular level. The growing understanding of the molecular pathways involved in cardiovascular diseases and the rapid progress in the development of targeted MRI contrast agents have created high expectations for the MRI-based in vivo visualization and quantification of molecular markers. Our research in this field of Molecular Imaging will focus on the use of Gd-DTPA-containing liposomes and dendrimers that are targeted to known as well as newly identified disease markers and on the development of MRI procedures for marker quantification. Whereas conventional MRI detects the outcome of disease processes, molecular MR imaging provides the opportunity to monitor those molecular routes that are at the basis of the disease, or play a critical role in the early response to treatment. A second line of research addresses the structure, function and physiology of skeletal muscle in mouse and rat. The muscle research is aimed to obtain a detailed understanding of the mechanistic basis of the development of clinically relevant disorders like muscle weakness and pressure sores. Muscle micro-structure is studied with the use of Diffusion Tensor Imaging, while contractile function is investigated with MRI tagging. Muscle physiology and metabolism are studied with a range of MRI and MRS techniques, including perfusion-sensitive MRI and multi-nuclear MRS for the measurement of muscle metabolism. The measured experimental MRI data serve to improve mathematical models that link local micro-structure and local contractile function. These models are used to predict the consequences of structural defects and prolonged loading. The MRS data are used to quantify the metabolic fluxes during contraction and, in particular, to model the activity of the mitochondrion because of its vital role in muscle energetics. The above lines of in vivo MR research in anaesthetized animals require state-of-the-art hardware. Since the 6.3 Tesla scanner is engaged in a multidisciplinary research program hat involves groups from a number of different academic institutions, financial support for the requested upgrade from national resources is justified.