application) The applicant's long term objectives are to develop and characterize Magnetic Resonance Imaging (MRI) techniques that will image tissue perfusion, and ultimately, provide a quantitative measure of it. The immediate aim is to continue the development of Steady State Free Precession (SSFP) MRI methods. First, a method will be theoretically developed and then programmed into a spectrometer. Then its flow sensitivity will be measured. The techniques to be developed and characterized are 1) Missing Pulse SSFP (MP-SSFP), 2) a three dimensional (3D) Fourier version of MP-SSFP where velocity is the third dimension and 3) a moving reference frame (MRF) technique. The first method, MP-SSFP, has already been developed and its slow flow (mm/s) sensitivity demonstrated in flow phantoms. Qualitative changes in its signal intensity have been observed as a function of perfusion rate in the isolated perfused rabbit kidney. However, the large background signal from static tissue in this method makes quantitation of the signal from flowing blood difficult. The 3D MP-SSFP technique will provide a quantitative velocity spectrum for each voxel of the image, thus separating out the static component of the signal and at the same time providing a quantitative measure of the flow. The MRF technique will be used to measure velocity distributions with a non-zero mean. The technique measures signal only from material moving with a speed near that of the MRF. Both the mean and width of the distribution of speeds to which the MRF is sensitive can be adjusted. The flow sensitivity will be characterized by using flow phantoms of gradually increasing complexity. Then the MRI techniques will be evaluated in isolated perfused rabbit kidneys. The in-vitro kidney has realistic biological flow, but its perfusion can be readily controlled. The MRI technique will then be tested in three in-vivo models: a) rabbit kidney, b) rabbit muscle, both fast and slow twitch under a variety of electrical stimulations, and c) rabbit brain in which a photochemically induced cortical perfusion defect has been created by end-capillary block. Standard measurements of the perfusion (by microspheres and/or rubidium) in regions of the kidney, brain and skeletal muscle in the rabbit models will be compared with those obtained with MRI. The last tests of a MRI method will be to determine which components of the flow in the isolated perfused rabbit kidney contribute to the observed MRI signal. This will be accomplished by pharmacological and mechanical manipulation.
