The magnetic susceptibility properties of endogenous iron and linewidth (LW) mapping and the newly acquired echo planar imaging technology (EPI) are used for validating a new MR parameter of biological function; that of oxygen consumption. Oxygen consumption (OC) is a fundamental parameter for assessing aerobic respiration that is not readily available without invasive central blood sampling techniques or positron emission tomography (PET). Global oxygen consumption (gOC) can be determined from blood flow (Q) and the blood arteriovenous oxygenation difference (AVOD) across an organ by application of the Fick principle (GOC=AVOD*Q). MR imaging can measure these parameters for organs such as brain, kidney and skeletal muscle which have blood vessels of suitable size, geometry and number for imaging. Theoxygenation state of static blood is readily determined from the transverse relaxation rate (R2=1/T2) of water. Correction for blood flow must be made for in vivo measurements of R2. Using flow compensation, measurements can be made by both conventional MRI and EPI techniques. EPI is intrinsically T2 sensitive and allows rapid measurement of transverse magnetization and hence blood oxygenation. Blood flow can be measured quantitatively from changes in the MR signal, particularly phase, with both conventional MR and EPI techniques. Pulse sequences using EPI have been designed to remove unwanted physiological motion to allow rapid independent measurement of blood flow and oxygenation state. Regional OC can be achieved with improved spatial resolution of smaller vessels, as is being explored in Core D. Another approach for measuring regional tissue oxygenation (rtO) for tissues within microscopic blood vessels is LW mapping in which changes in the magnetic susceptibility of tissue due to changes in venous blood volume and oxygenation state may be assessed by changes in LW reflecting changes in R2. EPI allows rapid measurement of Hahn offset spin echo images with multiple offsets which can be processed by Fourier Transform to yield the LW image. Tissue blood volume measurements use the methods being developed in Projects 1 and 2. These MR methods will be validated against the gold standards of central arteriovenous sampling and positron emission tomography (PET). Animal models are (a) the canine model of hypercapnia for cerebral flow modulation (as used in Project 1), and (b) the canine model of hypovolemia for flow and arteriovenous oxygen difference modulation in brain, kidney and muscle. Human studies of GOC and rto are integrated into the clinical PET-MR studies of cerebrovascular disease and neoplasia in Project 1.
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