A New Magnetic Resonance Imaging Console for the 7 Tesla Small Bore Animal Imaging Facility

This proposal to BBSRC is for new equipment to enable images to be taken of intact biological specimens ranging from isolated organs (including human heart tissue) through to living animals. The technology we will use is magnetic resonance imaging (MRI), which is a non-destructive method to take images of superb clarity and detail from within living subjects without using harmful radiation. MRI is widely used for imaging patients in hospitals, and we are proposing to purchase similar equipment for imaging much smaller subjects, such as rats and mice. One of the advantages of MRI is that it is a very versatile technique which can be used in a number of different ways / in this proposal we include three different studies of the brain: one in which we look for regions of the brain which are important in regulating appetite; another in which we are interested in where drugs which alter states of mind act; and a third in which we wish to understand how inflammation (the process by which the body responds to an infection or allergy) affects the brain. We are not restricting our study to the brain / we will also use imaging to find out about detailed structure of the heart, to discover mechanisms which lead to the formation of new blood vessels, and finally by imaging, after death, the heads of a number of specimens of different mammalian species (including some valuable samples stored in museums) we hope to improve our understanding of how mammals move and maintain their balance. The versatility of the technique means that it can be used to help provide answers to a large range of scientific questions in biology, and by this purchase we will be able to provide the opportunity to local researchers to undertake state-of-the-art imaging studies for several years to come.

This proposal is to support the purchase of a new MRI console to be interfaced to an existing horizontal bore 7 T animal imaging magnet. It will be used to continue funded research in a number of collaborations in neuroscience and cardiovascular research. We will use pharmacological challenge functional MRI (pMRI) in two projects / one in which we will probe appetite control in the brain and the other in which we will investigate how inhibition of the NMDA receptor exerts downstream effects on other neurotransmitter systems. In appetite regulation, it is an open question as to how homeostatic and hedonistic mechanisms interact to control eating behaviour, and we will use pMRI together with specific pharmacological challenges to identify the brain areas and neurotransmitter systems which are involved in these two processes. We will then use these data to interpret how ghrelin / the putative 'hunger' signal acts. We will use sub-anaesthetic doses of ketamine to inhibit NMDA activity in vivo, and by combining this with pre-treatment with other agents and comparing to a more potent inhibitor, phencyclidine, we will test the hypothesis that NMDA inhibition exerts downstream effects through paradoxically stimulating glutamate release. A third neuroscience project in vivo will use pMRI to characterize the effects of inflammatory mediators, in particular to determine their interaction with glutamate neurotransmission. Structural imaging of fixed specimens will be used in a comparative biology project to understand the vestibular-ocular reflex and how it develops in different ways in different mammals. In cardiovascular science we will use structural and diffusion weighted imaging of fixed hearts to provide data to generate 3-D biophysical models of the heart, and in the final project dynamic contrast enhanced imaging will be used to characterize molecular and genetic signals which control angiogenesis.