The goal of this project is to develop methods for studying blood perfusion and oxygen tension in the brain using magnetic resonance imaging (MRI) of fluorinated blood substitutes (FBS), and to compare the results with those obtained using several techniques which have been proposed using proton MRI. The major issue is the possibility and desirability of detecting blood flow at the microvessel level, i.e., arterioles, capillaries, and venules. Conventional proton MRI has the major problem that the overwhelming majority of the proton spins come from extravascular water, so that getting adequate suppression of the stationary spins is difficult. Furthermore, most proton MRI flow studies to date have focussed on detecting flow in the major vessels, and methods which may be able to detect microvessel flow are still embryonic. Hence, at present the validity of these proton MRI perfusion techniques is questionable. Fluorine 19 FBS MRI has the unique advantage that the MRI signal comes only from the vascular system, so that the problem of suppressing static spins does not exist. Furthermore, our previous work has shown that FBS MRI can be used to map the mean vascular oxygen tension in vivo. We address the problem of hcw to make FBS MRI sensitive to flow phenomena at the microvessel level, i.e., with velocities less than 1 millimeter per second. We also address the problem of distinguishing the time dependence of the MRI signal due to flow induced washin/washout phenomena from the time dependence of oxygen induced T1 relaxation. We propose to compare quantitative MRI measurements of local blood flow in the cat brain with measurements made using the established technique of radioactive microspheres. We also prcpose qualitative comparison of the microvessel flow velocity field with that demonstrated using autoradiography of 14-C LAP. These results will be compared with several proposed echniques to image caillary flow using proton MRI. As a continuation of our previous work in this field, we intend to evaluate more fluorocarbon compounds in our search for improved biological and physical characteristics needed for FBS MRI.
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